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]

Link to SEPIO compliant JSON-LD document

Variant: NM_004333.6(BRAF):c.1433-19A>G

CA232434

136532 (ClinVar)

Gene: BRAF

Condition: RASopathy

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 32508ced-9033-4f01-b4c7-f8b4db5a4307

Approved on: 2024-09-17

Published on: 2024-10-01

HGVS expressions

NM_004333.6:c.1433-19A>G

NM_004333.6(BRAF):c.1433-19A>G

NC_000007.14:g.140778094T>C

CM000669.2:g.140778094T>C

NC_000007.13:g.140477894T>C

CM000669.1:g.140477894T>C

NC_000007.12:g.140124363T>C

NG_007873.3:g.151671A>G

ENST00000646891.2:c.1433-19A>G

ENST00000288602.11:c.1553-19A>G

ENST00000479537.6:c.103-19A>G

ENST00000496384.7:c.1433-19A>G

ENST00000497784.2:c.*883-19A>G

ENST00000642228.1:c.*511-19A>G

ENST00000642875.1:n.997-19A>G

ENST00000644120.1:n.1823-19A>G

ENST00000644650.1:c.529-19A>G

ENST00000644905.1:n.1522-19A>G

ENST00000644969.2:c.1553-19A>G

ENST00000646730.1:c.1433-19A>G

ENST00000646891.1:c.1433-19A>G

ENST00000647434.1:c.476-19A>G

ENST00000288602.10:c.1433-19A>G

ENST00000496384.6:c.256-19A>G

ENST00000497784.1:c.1468-19A>G

NM_004333.4:c.1433-19A>G

NM_001354609.1:c.1433-19A>G

NM_004333.5:c.1433-19A>G

NR_148928.1:n.1738-19A>G

NM_001354609.2:c.1433-19A>G

NM_001374244.1:c.1553-19A>G

NM_001374258.1:c.1553-19A>G

NM_001378467.1:c.1442-19A>G

NM_001378468.1:c.1433-19A>G

NM_001378469.1:c.1367-19A>G

NM_001378470.1:c.1331-19A>G

NM_001378471.1:c.1322-19A>G

NM_001378472.1:c.1277-19A>G

NM_001378473.1:c.1277-19A>G

NM_001378474.1:c.1433-19A>G

NM_001378475.1:c.1169-19A>G

Benign

BP4 BP7 BP5 BA1

Evidence Links 0

Expert Panel

RASopathy VCEP

Criteria Specification Information

Criteria Specification: ClinGen RASopathy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for BRAF Version 2.1.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

RASopathy VCEP

The c.1433-19A>G in BRAF is an intronic variant located in intron 11. The minor allele frequency of this variant in gnomAD v4 is 0.2572% (3030/1178128) in the European (non-Finnish) population, which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen RASopathy Expert panel for autosomal dominant RASopathy variants (BA1). This variant is not predicted by SpliceAI to impact splicing. In addition, it occurs at a nucleotide that is not conserved (BP4, BP7). This variant has been identified in at least 2 patients with clinical features of a RASopathy (PS4_Supporting not met; GeneDx, Greenwood Genetics, Otto von Guericke University Magdeburg, internal data, GTR ID's: 26957, 1019; ClinVar SCV000207632.1, SCV000167210.14). However, this variant has been identified in a patient with an alternate molecular basis for disease (BP5; GeneDx internal data, GTR ID's: 26957; ClinVar SCV000167210.14). In summary, this variant meets criteria to be classified as benign for autosomal dominant RASopathies based on the ACMG/AMP criteria applied, as specified by the ClinGen RASopathy Variant Curation Expert Panel: BA1, BP4, BP5, BP7 (Specification Version 2.1, 9/17/2024)

BP4

This variant is not predicted by SpliceAI to impact splicing

BP7

This variant is a synonymous (silent) variant that occurs at a nucleotide that is not conserved

BP5

This variant has been identified in a patient with an alternate molecular basis for disease (BP5; GeneDx internal data, GTR ID's: 26957; ClinVar SCV000167210.14).

BA1

The minor allele frequency of this variant in gnomAD v4 is 0.2572% (3030/1178128) in the European (non-Finnish) population

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