Research workflows

What does CFTR p.Phe508del change?

Normalize an allele, compare transcript consequences and separate VEP annotation from ClinVar classification.

Ask your AI client

Use GeneFoundry to annotate NM_000492.4:c.1521_1523del in CFTR on GRCh38. Show the returned VCF, genomic HGVS and SPDI representations. Identify the MANE Select transcript, consequence term and protein change, then compare one alternative transcript. Find the matching ClinVar record and report its classification, review status and transcript version separately. Flag identifier or normalization differences before joining records; do not turn VEP impact labels into an ACMG classification.
Connect GeneFoundry first

The result

VEP returned an in-frame deletion and confirmed NM_000492.4 as MANE Select. The same gene and cDNA-change search found ClinVar VCV000007105, labeled pathogenic with a practice-guideline review status. These are separate annotation and classification outputs.

Allele identity and coordinate conventions
FieldReturned value
InputNM_000492.4:c.1521_1523del
AssemblyGRCh38
VEP VCF spelling7-117559591-TCTT-T
Genomic HGVSNC_000007.14:g.117559592_117559594del
SPDINC_000007.14:117559591:CTT:
ClinVar VCF spelling7-117559590-ATCT-A
One allele, two transcript annotations
TranscriptContextConsequenceProtein change
ENST00000003084.11MANE Select: NM_000492.4inframe_deletionENSP00000003084.6:p.Phe508del
ENST00000426809.5Alternative protein-coding transcriptinframe_deletionENSP00000389119.1:p.Phe478del
ClinVar assertion, reported separately
FieldReturned value
RecordVCV000007105
Record nameNM_000492.3(CFTR):c.1521_1523del (p.Phe508del)
Aggregate classificationPathogenic
Review statusPractice guideline · 4 stars
Source last evaluatedMar 03, 2004

The ClinVar record uses NM_000492.3 in its name, whereas VEP marks NM_000492.4 as MANE Select. The direct versioned ClinVar lookup returned no match; a gene-plus-change search located the accession.

VEP and ClinVar coordinate spellings differ. HGVS, SPDI and VCF use different conventions; retain both source representations and normalize before an automated join.

The ClinVar classification is an aggregate record label. Review condition-specific assertions before applying it to a particular disorder.

The transcript table selects two returned protein-coding annotations, not the entire VEP transcript list. No ACMG criteria are assigned here.

ClinVar release: 31 August 2026. Its release date and star rating do not mean that every assertion was reevaluated recently. VEP supplies retrieval provenance but no upstream release number in this response.

Retrieved through Claude Code 2.1.261 · Claude Opus 5.

Original source records
How GeneFoundry got this

  1. Annotate the transcript HGVS

    Start with the supplied transcript version and explicit GRCh38 assembly. VEP returns an allele representation and a prioritized transcript.

    vep_annotate_variant

    {
  "variant": "NM_000492.4:c.1521_1523del",
  "assembly": "GRCh38",
  "response_mode": "compact"
}

  2. Locate the ClinVar record

    The exact versioned HGVS lookup found no indexed record. Search the gene and cDNA change, then inspect the returned accession.

    clinvar_search_variants

    {
  "query": "c.1521_1523del",
  "gene_symbol": "CFTR",
  "limit": 5,
  "response_mode": "compact",
  "request_id": "genefoundry-cftr-f508del-clinvar-03"
}

  3. Read the source classification

    Retrieve the matched ClinVar accession and preserve its transcript version, assembly, review status and coordinates.

    clinvar_get_variant

    {
  "identifier": "VCV000007105",
  "id_type": "vcv",
  "response_mode": "standard",
  "request_id": "genefoundry-cftr-f508del-clinvar-04"
}

  4. Record alternative representations

    Ask the Variant Recoder for genomic HGVS, SPDI and VCF spellings using the original transcript HGVS.

    vep_recode_variant

    {
  "variants": [
    "NM_000492.4:c.1521_1523del"
  ],
  "assembly": "GRCh38",
  "fields": "hgvsg,spdi,vcf_string"
}

  5. Confirm the relevant transcript

    Inspect the full VEP annotation for MANE Select and one alternative protein-coding transcript.

    vep_annotate_variant

    {
  "variant": "7-117559591-TCTT-T",
  "assembly": "GRCh38",
  "response_mode": "full"
}

One small deletion on one assembly is shown; structural variants and other reference assemblies need their own supported queries.

Consequence terms describe predicted sequence effects. MODERATE is a VEP impact category, not an ACMG evidence strength or a clinical classification.

ClinVar and VEP returned different VCF spellings. Preserve their provenance and normalize against the same reference before automated record matching.

Try it with your clientMore research workflows