rs6944385

chr7-140914587-A-T

Variant summary

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

The NM_001374258.1(BRAF):c.138+9979T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 152,036 control chromosomes in the GnomAD database, including 10,934 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 (10934 hom., cov: 30)
• Consequence: BRAF NM_001374258.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.330

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.662 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRAF	NM_001374258.1	c.138+9979T>A		intron_variant		ENST00000644969.2
BRAF	NM_004333.6	c.138+9979T>A		intron_variant		ENST00000646891.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRAF	ENST00000644969.2	c.138+9979T>A		intron_variant			NM_001374258.1
BRAF	ENST00000646891.2	c.138+9979T>A		intron_variant			NM_004333.6	P4

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45507 AN: 151918 Hom.: 10885 Cov.: 30

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.274

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

GnomAD4 genome AF: 0.300 AC: 45605 AN: 152036 Hom.: 10934 Cov.: 30 AF XY: 0.297 AC XY: 22117 AN XY: 74344

Gnomad4 AFR AF: 0.669

Gnomad4 AMR AF: 0.182

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.174

Gnomad4 SAS AF: 0.310

Gnomad4 FIN AF: 0.152

Gnomad4 NFE AF: 0.143

Gnomad4 OTH AF: 0.274

Alfa AF: 0.232 Hom.: 876

Bravo AF: 0.315

Asia WGS AF: 0.275 AC: 956 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	4.8
Dann	Benign	0.61

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: rs6944385; hg19: chr7-140614387;