7-140914412-A-T

Variant names:

• chr7-140914412-A-T
• rs11762469
• NM_001374258.1:c.138+10154T>A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_004333.6(BRAF):​c.138+10154T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 152,066 control chromosomes in the GnomAD database, including 13,286 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 0.37 (13286 hom., cov: 32)
• Consequence: BRAF NM_004333.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.109

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRAF	NM_001374258.1	c.138+10154T>A		intron_variant	Intron 1 of 19	ENST00000644969.2	NP_001361187.1
BRAF	NM_004333.6	c.138+10154T>A		intron_variant	Intron 1 of 17	ENST00000646891.2	NP_004324.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRAF	ENST00000644969.2	c.138+10154T>A		intron_variant	Intron 1 of 19		NM_001374258.1	ENSP00000496776.1
BRAF	ENST00000646891.2	c.138+10154T>A		intron_variant	Intron 1 of 17		NM_004333.6	ENSP00000493543.1

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55869 AN: 151950 Hom.: 13289 Cov.: 32

Gnomad AFR AF: 0.0989

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.543

Gnomad OTH AF: 0.395

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

GnomAD4 genome AF: 0.367 AC: 55856 AN: 152066 Hom.: 13286 Cov.: 32 AF XY: 0.361 AC XY: 26820 AN XY: 74324

Gnomad4 AFR AF: 0.0987

Gnomad4 AMR AF: 0.334

Gnomad4 ASJ AF: 0.403

Gnomad4 EAS AF: 0.158

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.502

Gnomad4 NFE AF: 0.543

Gnomad4 OTH AF: 0.392

Alfa AF: 0.304 Hom.: 941

Bravo AF: 0.345

Asia WGS AF: 0.171 AC: 595 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.9
DANN	Benign	0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.27		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.26		Position offset: 27
DS_DG_spliceai		0.27		Position offset: -46

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

Publications

LitVar

Other links and lift over

dbSNP: rs11762469; hg19: chr7-140614212;