Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_002880.3(RAF1):c.639T>C (p.Thr213=)

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Curation History
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CA134743

44629 (ClinVar)

Gene: RAF1

Condition: RASopathy

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 424749f9-713c-4d2c-9ad5-fb564c0ec802

Approved on: 2019-11-04

Published on: 2019-11-04

HGVS expressions

NM_002880.3:c.639T>C

NM_002880.3(RAF1):c.639T>C (p.Thr213=)

NC_000003.12:g.12606242A>G

CM000665.2:g.12606242A>G

NC_000003.11:g.12647741A>G

CM000665.1:g.12647741A>G

NC_000003.10:g.12622741A>G

NG_007467.1:g.62938T>C

NM_001354689.1:c.639T>C

NM_001354690.1:c.639T>C

NM_001354691.1:c.396T>C

NM_001354692.1:c.396T>C

NM_001354693.1:c.582-1953T>C

NM_001354694.1:c.396T>C

NM_001354695.1:c.339-1953T>C

NR_148940.1:n.1054T>C

NR_148941.1:n.1054T>C

NR_148942.1:n.1054T>C

ENST00000251849.8:c.639T>C

ENST00000416093.1:c.*259-1953T>C

ENST00000423275.5:c.*316T>C

ENST00000432427.2:n.318-1953T>C

ENST00000442415.6:c.639T>C

ENST00000491290.1:n.160T>C

Benign

BP7 BP5 BP4 BA1

Evidence Links 0

Expert Panel

RASopathy VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

RASopathy VCEP

The c.639T>C (p.Thr213Thr) variant in RAF1 is classified as benign because it has been identified in 0.05616% (lower bound of the 95% CI of 28/35434) of Latino alleles in gnomAD (BA1; https://gnomad.broadinstitute.org). It was observed in an individual with an alternate molecular basis for disease (BP5; SCV000061357.6). It does not alter an amino acid residue, is not located within the splice consensus site, and computational splice prediction tools do not predict an impact to splicing (BP4, BP7). ACMG/AMP Criteria applied: BA1, BP4, BP5, BP7.

BP7

Splicing is not predicted to be impacted in Alamut. Silent change conserves amino acid. Alamut indicates the base is not highly conserved.

BP5

LMM internal data (SCV000061357.6): observed in a 1yo male proband who was heterozygous for PTPN11c.1472C>T (p.Pro491Leu), which is pathogenic in ClinVar

BP4

Splicing not predicted to be impacted in Alamut. REVEL score not provided for silent variant.

BA1

Present in 0.05616% (95% CI of 28/35434) of Latino alleles in gnomAD.

Curation History

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