7-140799307-C-T

Position:

• chr7-140799307-C-T

Variant summary

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

The NM_001374258.1(BRAF):​c.980+1055G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 232,174 control chromosomes in the GnomAD database, including 21,838 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 (13201 hom., cov: 32)
  • Exomes 𝑓: 0.43 (8637 hom.)
• Consequence: BRAF NM_001374258.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.129

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRAF	NM_001374258.1	c.980+1055G>A		intron_variant		ENST00000644969.2	NP_001361187.1
BRAF	NM_004333.6	c.980+1055G>A		intron_variant		ENST00000646891.2	NP_004324.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRAF	ENST00000644969.2	c.980+1055G>A		intron_variant			NM_001374258.1	ENSP00000496776
BRAF	ENST00000646891.2	c.980+1055G>A		intron_variant			NM_004333.6	ENSP00000493543	P4

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55680 AN: 151888 Hom.: 13204 Cov.: 32

Gnomad AFR AF: 0.0988

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.541

Gnomad OTH AF: 0.395

GnomAD4 exome AF: 0.429 AC: 34386 AN: 80168 Hom.: 8637 Cov.: 0 AF XY: 0.435 AC XY: 16036 AN XY: 36864

Gnomad4 AFR exome AF: 0.0933

Gnomad4 AMR exome AF: 0.294

Gnomad4 ASJ exome AF: 0.406

Gnomad4 EAS exome AF: 0.112

Gnomad4 SAS exome AF: 0.201

Gnomad4 FIN exome AF: 0.452

Gnomad4 NFE exome AF: 0.539

Gnomad4 OTH exome AF: 0.435

GnomAD4 genome AF: 0.366 AC: 55667 AN: 152006 Hom.: 13201 Cov.: 32 AF XY: 0.360 AC XY: 26717 AN XY: 74274

Gnomad4 AFR AF: 0.0985

Gnomad4 AMR AF: 0.333

Gnomad4 ASJ AF: 0.403

Gnomad4 EAS AF: 0.156

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.502

Gnomad4 NFE AF: 0.541

Gnomad4 OTH AF: 0.392

Alfa AF: 0.500 Hom.: 35749

Bravo AF: 0.344

Asia WGS AF: 0.171 AC: 595 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.1
DANN	Benign	0.71

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: rs10487888; hg19: chr7-140499107;