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_002880.3(RAF1):c.680+6T>C

CA134749

44630 (ClinVar)

Gene: RAF1

Condition: RASopathy

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 347868b5-7cc2-4bd0-ba83-bc69847e7691

Approved on: 2019-07-25

Published on: 2019-12-03

HGVS expressions

NM_002880.3:c.680+6T>C

NM_002880.3(RAF1):c.680+6T>C

NC_000003.12:g.12606195A>G

CM000665.2:g.12606195A>G

NC_000003.11:g.12647694A>G

CM000665.1:g.12647694A>G

NC_000003.10:g.12622694A>G

NG_007467.1:g.62985T>C

NM_001354689.1:c.680+6T>C

NM_001354690.1:c.680+6T>C

NM_001354691.1:c.437+6T>C

NM_001354692.1:c.437+6T>C

NM_001354693.1:c.582-1906T>C

NM_001354694.1:c.437+6T>C

NM_001354695.1:c.339-1906T>C

NR_148940.1:n.1095+6T>C

NR_148941.1:n.1095+6T>C

NR_148942.1:n.1095+6T>C

ENST00000251849.8:c.680+6T>C

ENST00000416093.1:c.*259-1906T>C

ENST00000423275.5:c.*357+6T>C

ENST00000432427.2:n.318-1906T>C

ENST00000442415.6:c.680+6T>C

ENST00000491290.1:n.201+6T>C

Likely Benign

BP4 BP7

BS1

Evidence Links 0

Expert Panel

RASopathy VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

RASopathy VCEP

Computational prediction tools and conservation analysis suggest that the c.680+6T>C variant in the RAF1 gene does not impact the protein (BP4). This is an intronic variant at a nucleotide that is not highly conserved and is not predicted to impact splicing (BP7). In addition, this variant is observed in many individuals in the normal population suggesting it is an unlikely cause of a RASopathy (BS1 not met). In summary, this variant meets criteria to be classified as likely benign. RASopathy-specific ACMG/AMP criteria applied (PMID:29493581): BP4, BP7.

BP4

No predicted splicing impact and located in a poorly conserved position.

BP7

Intronic non-coding variant in a poorly conserved position

BS1

Present in .019% (34/129096 CI 95%) of European non-Finnish alleles in gnomAD

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.