rs1639675

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004333.6(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_004333.6 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.672

Publications

6 publications found
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]
BRAF Gene-Disease associations (from GenCC):
  • cardiofaciocutaneous syndrome
    Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
  • cardiofaciocutaneous syndrome 1
    Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics, G2P, Genomics England PanelApp
  • LEOPARD syndrome 3
    Inheritance: AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp
  • Noonan syndrome 7
    Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P, Ambry Genetics, Genomics England PanelApp
  • Noonan syndrome
    Inheritance: AD Classification: MODERATE Submitted by: ClinGen
  • Noonan syndrome with multiple lentigines
    Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: ClinGen, Orphanet
  • anaplastic astrocytoma
    Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
  • Costello syndrome
    Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank MANE Protein UniProt
BRAFNM_001374258.1 linkc.981-2296A>G intron_variant Intron 7 of 19 ENST00000644969.2 NP_001361187.1
BRAFNM_004333.6 linkc.981-2296A>G intron_variant Intron 7 of 17 ENST00000646891.2 NP_004324.2 P15056

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BRAFENST00000644969.2 linkc.981-2296A>G intron_variant Intron 7 of 19 NM_001374258.1 ENSP00000496776.1 A0A2R8Y8E0
BRAFENST00000646891.2 linkc.981-2296A>G intron_variant Intron 7 of 17 NM_004333.6 ENSP00000493543.1 P15056

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
African (AFR)
AF:
0.145
AC:
6040
AN:
41516
American (AMR)
AF:
0.0687
AC:
1051
AN:
15296
Ashkenazi Jewish (ASJ)
AF:
0.0911
AC:
316
AN:
3470
East Asian (EAS)
AF:
0.0902
AC:
467
AN:
5178
South Asian (SAS)
AF:
0.192
AC:
926
AN:
4822
European-Finnish (FIN)
AF:
0.0938
AC:
995
AN:
10606
Middle Eastern (MID)
AF:
0.122
AC:
36
AN:
294
European-Non Finnish (NFE)
AF:
0.0697
AC:
4741
AN:
68008
Other (OTH)
AF:
0.0972
AC:
205
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
671
1343
2014
2686
3357
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
168
336
504
672
840
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0842
Hom.:
79
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
PhyloP100
-0.67
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

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