7-140734774-CAAAAAA-CAAAAAAAAAAAAAAAAA

Position:

• chr7-140734774-CAAAAAA-CAAAAAAAAAAAAAAAAA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_004333.6(BRAF):​c.2128-15_2128-5dupTTTTTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000284 in 773,528 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000041 (0 hom., cov: 27)
  • Exomes 𝑓: 0.000028 (0 hom.)
• Consequence: BRAF NM_004333.6 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19

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]

BRAF (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 21 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRAF	NM_001374258.1	c.2248-15_2248-5dupTTTTTTTTTTT		splice_region_variant, intron_variant		ENST00000644969.2	NP_001361187.1
BRAF	NM_004333.6	c.2128-15_2128-5dupTTTTTTTTTTT		splice_region_variant, intron_variant		ENST00000646891.2	NP_004324.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRAF	ENST00000644969.2	c.2248-15_2248-5dupTTTTTTTTTTT		splice_region_variant, intron_variant			NM_001374258.1	ENSP00000496776.1
BRAF	ENST00000646891.2	c.2128-15_2128-5dupTTTTTTTTTTT		splice_region_variant, intron_variant			NM_004333.6	ENSP00000493543.1

Frequencies

GnomAD3 genomes AF: 0.0000409 AC: 1 AN: 24448 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000766

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000280 AC: 21 AN: 749080 Hom.: 0 Cov.: 28 AF XY: 0.0000371 AC XY: 14 AN XY: 377198

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000450

Gnomad4 SAS exome AF: 0.000138

Gnomad4 FIN exome AF: 0.0000422

Gnomad4 NFE exome AF: 0.0000221

Gnomad4 OTH exome AF: 0.0000324

GnomAD4 genome AF: 0.0000409 AC: 1 AN: 24448 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 11460

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000766

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs373442098; hg19: chr7-140434574;