7-140785890-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001374258.1(BRAF):c.1178-82G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 397,150 control chromosomes in the GnomAD database, including 15,407 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 0.30 (10783 hom., cov: 32)
  • Exomes 𝑓: 0.17 (4624 hom.)
• Consequence: BRAF NM_001374258.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.78

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRAF	NM_001374258.1	c.1178-82G>A		intron_variant		ENST00000644969.2
BRAF	NM_004333.6	c.1177+1658G>A		intron_variant		ENST00000646891.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRAF	ENST00000644969.2	c.1178-82G>A		intron_variant			NM_001374258.1
BRAF	ENST00000646891.2	c.1177+1658G>A		intron_variant			NM_004333.6	P4
	ENST00000700122.1	n.503-8395C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45231 AN: 151856 Hom.: 10734 Cov.: 32

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.309

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.268

GnomAD4 exome AF: 0.169 AC: 41347 AN: 245176 Hom.: 4624 AF XY: 0.165 AC XY: 20561 AN XY: 124284

Gnomad4 AFR exome AF: 0.650

Gnomad4 AMR exome AF: 0.152

Gnomad4 ASJ exome AF: 0.202

Gnomad4 EAS exome AF: 0.138

Gnomad4 SAS exome AF: 0.305

Gnomad4 FIN exome AF: 0.135

Gnomad4 NFE exome AF: 0.147

Gnomad4 OTH exome AF: 0.211

GnomAD4 genome AF: 0.298 AC: 45329 AN: 151974 Hom.: 10783 Cov.: 32 AF XY: 0.296 AC XY: 21981 AN XY: 74298

Gnomad4 AFR AF: 0.664

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.198

Gnomad4 EAS AF: 0.173

Gnomad4 SAS AF: 0.308

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.268

Alfa AF: 0.187 Hom.: 1890

Bravo AF: 0.312

Asia WGS AF: 0.277 AC: 963 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
Cadd	Benign	14
Dann	Benign	0.45

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: rs1267646; hg19: chr7-140485690; COSMIC: COSV56111046; COSMIC: COSV56111046;