rs1639675

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001374258.1(BRAF):​c.981-2296A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0975 in 152,212 control chromosomes in the GnomAD database, including 786 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.097 ( 786 hom., cov: 32)

Consequence

BRAF
NM_001374258.1 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.672
Variant links:
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 -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BRAFNM_001374258.1 linkuse as main transcriptc.981-2296A>G intron_variant ENST00000644969.2
BRAFNM_004333.6 linkuse as main transcriptc.981-2296A>G intron_variant ENST00000646891.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BRAFENST00000644969.2 linkuse as main transcriptc.981-2296A>G intron_variant NM_001374258.1
BRAFENST00000646891.2 linkuse as main transcriptc.981-2296A>G intron_variant NM_004333.6 P4

Frequencies

GnomAD3 genomes
AF:
0.0975
AC:
14828
AN:
152094
Hom.:
786
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.146
Gnomad AMI
AF:
0.0669
Gnomad AMR
AF:
0.0689
Gnomad ASJ
AF:
0.0911
Gnomad EAS
AF:
0.0896
Gnomad SAS
AF:
0.193
Gnomad FIN
AF:
0.0938
Gnomad MID
AF:
0.117
Gnomad NFE
AF:
0.0697
Gnomad OTH
AF:
0.0963
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0975
AC:
14838
AN:
152212
Hom.:
786
Cov.:
32
AF XY:
0.100
AC XY:
7445
AN XY:
74430
show subpopulations
Gnomad4 AFR
AF:
0.145
Gnomad4 AMR
AF:
0.0687
Gnomad4 ASJ
AF:
0.0911
Gnomad4 EAS
AF:
0.0902
Gnomad4 SAS
AF:
0.192
Gnomad4 FIN
AF:
0.0938
Gnomad4 NFE
AF:
0.0697
Gnomad4 OTH
AF:
0.0972
Alfa
AF:
0.0806
Hom.:
66
Bravo
AF:
0.0935
Asia WGS
AF:
0.140
AC:
486
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
0.38
DANN
Benign
0.82

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1639675; hg19: chr7-140496563; COSMIC: COSV56181035; COSMIC: COSV56181035; API