rs3748093

Positions:

• chr7-140800651-T-A
• chr7-140800651-T-C
• chr7-140800651-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004333.6(BRAF):​c.861-170A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0182 in 152,326 control chromosomes in the GnomAD database, including 156 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Genomes: 𝑓 0.018 (156 hom., cov: 32)
• Consequence: BRAF NM_004333.6 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.100

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 7-140800651-T-A is Benign according to our data. Variant chr7-140800651-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 1207147.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRAF	NM_001374258.1	c.861-170A>T		intron_variant		ENST00000644969.2	NP_001361187.1
BRAF	NM_004333.6	c.861-170A>T		intron_variant		ENST00000646891.2	NP_004324.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRAF	ENST00000644969.2	c.861-170A>T		intron_variant			NM_001374258.1	ENSP00000496776
BRAF	ENST00000646891.2	c.861-170A>T		intron_variant			NM_004333.6	ENSP00000493543	P4

Frequencies

GnomAD3 genomes AF: 0.0182 AC: 2767 AN: 152208 Hom.: 154 Cov.: 32

Gnomad AFR AF: 0.00227

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0750

Gnomad ASJ AF: 0.0121

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.0103

Gnomad FIN AF: 0.0308

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00282

Gnomad OTH AF: 0.0138

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

GnomAD4 genome AF: 0.0182 AC: 2769 AN: 152326 Hom.: 156 Cov.: 32 AF XY: 0.0213 AC XY: 1587 AN XY: 74490

Gnomad4 AFR AF: 0.00226

Gnomad4 AMR AF: 0.0753

Gnomad4 ASJ AF: 0.0121

Gnomad4 EAS AF: 0.170

Gnomad4 SAS AF: 0.0104

Gnomad4 FIN AF: 0.0308

Gnomad4 NFE AF: 0.00282

Gnomad4 OTH AF: 0.0137

Alfa AF: 0.00953 Hom.: 7

Bravo AF: 0.0237

Asia WGS AF: 0.0700 AC: 243 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	May 14, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.7
DANN	Benign	0.20
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3748093; hg19: chr7-140500451;