rs1267636

chr7-140792239-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001374258.1(BRAF):c.1140+2069A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 152,190 control chromosomes in the GnomAD database, including 1,155 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 0.11 (1155 hom., cov: 32)
• Consequence: BRAF NM_001374258.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.39

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRAF	NM_001374258.1	c.1140+2069A>G		intron_variant		ENST00000644969.2
BRAF	NM_004333.6	c.1140+2069A>G		intron_variant		ENST00000646891.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRAF	ENST00000644969.2	c.1140+2069A>G		intron_variant			NM_001374258.1
BRAF	ENST00000646891.2	c.1140+2069A>G		intron_variant			NM_004333.6	P4
	ENST00000700122.1	n.503-2046T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.112 AC: 16980 AN: 152072 Hom.: 1152 Cov.: 32

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.0771

Gnomad ASJ AF: 0.0950

Gnomad EAS AF: 0.0893

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.0938

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0706

Gnomad OTH AF: 0.109

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.112 AC: 17014 AN: 152190 Hom.: 1155 Cov.: 32 AF XY: 0.114 AC XY: 8486 AN XY: 74422

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.0769

Gnomad4 ASJ AF: 0.0950

Gnomad4 EAS AF: 0.0899

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.0938

Gnomad4 NFE AF: 0.0706

Gnomad4 OTH AF: 0.110

Alfa AF: 0.0920 Hom.: 128

Bravo AF: 0.110

Asia WGS AF: 0.146 AC: 506 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	3.7
Dann	Benign	0.66

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

Other links and lift over

dbSNP: rs1267636; hg19: chr7-140492039; COSMIC: COSV56181027;