rs397516901
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_001374258.1(BRAF):āc.2349T>Cā(p.Phe783=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,613,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 31)
Exomes š: 0.000014 ( 0 hom. )
Consequence
BRAF
NM_001374258.1 synonymous
NM_001374258.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.17
Genes affected
BRAF (HGNC:1097): (B-Raf proto-oncogene, serine/threonine kinase) This gene encodes a protein belonging to the RAF family of serine/threonine protein kinases. This protein plays a role in regulating the MAP kinase/ERK signaling pathway, which affects cell division, differentiation, and secretion. Mutations in this gene, most commonly the V600E mutation, are the most frequently identified cancer-causing mutations in melanoma, and have been identified in various other cancers as well, including non-Hodgkin lymphoma, colorectal cancer, thyroid carcinoma, non-small cell lung carcinoma, hairy cell leukemia and adenocarcinoma of lung. Mutations in this gene are also associated with cardiofaciocutaneous, Noonan, and Costello syndromes, which exhibit overlapping phenotypes. A pseudogene of this gene has been identified on the X chromosome. [provided by RefSeq, Aug 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP6
?
Variant 7-140734669-A-G is Benign according to our data. Variant chr7-140734669-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 44824.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=1.17 with no splicing effect.
BS2
?
High AC in GnomAdExome4 at 20 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BRAF | NM_001374258.1 | c.2349T>C | p.Phe783= | synonymous_variant | 19/20 | ENST00000644969.2 | |
BRAF | NM_004333.6 | c.2229T>C | p.Phe743= | synonymous_variant | 18/18 | ENST00000646891.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BRAF | ENST00000644969.2 | c.2349T>C | p.Phe783= | synonymous_variant | 19/20 | NM_001374258.1 | |||
BRAF | ENST00000646891.2 | c.2229T>C | p.Phe743= | synonymous_variant | 18/18 | NM_004333.6 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 151868Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251490Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135920
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GnomAD4 exome AF: 0.0000137 AC: 20AN: 1461886Hom.: 0 Cov.: 33 AF XY: 0.0000179 AC XY: 13AN XY: 727244
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GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 151868Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74178
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jan 31, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 06, 2012 | Phe743Phe in exon 18 of BRAF: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and it is not located w ithin the splice consensus sequence. - |
RASopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Feb 06, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at