rs1267622

Variant names:

• chr7-140828517-A-G
• rs1267622
• NM_001374258.1:c.504+6092T>C

Your query was ambiguous. Multiple possible variants found:

• chr7-140828517-A-G
• chr7-140828517-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001374258.1(BRAF):​c.504+6092T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 152,078 control chromosomes in the GnomAD database, including 18,135 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 0.41 (18135 hom., cov: 32)
• Consequence: BRAF NM_001374258.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0620
• Publications: 10 publications found

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 Gene-Disease associations (from GenCC):

• cardiofaciocutaneous syndrome

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• cardiofaciocutaneous syndrome 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics, G2P, Genomics England PanelApp
• LEOPARD syndrome 3

  Inheritance: AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp
• Noonan syndrome 7

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P, Ambry Genetics, Genomics England PanelApp
• Noonan syndrome

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen
• Noonan syndrome with multiple lentigines

  Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: ClinGen, Orphanet
• anaplastic astrocytoma

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• Costello syndrome

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 = 0.82 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRAF	NM_001374258.1	c.504+6092T>C		intron_variant	Intron 3 of 19	ENST00000644969.2	NP_001361187.1
BRAF	NM_004333.6	c.504+6092T>C		intron_variant	Intron 3 of 17	ENST00000646891.2	NP_004324.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRAF	ENST00000644969.2	c.504+6092T>C		intron_variant	Intron 3 of 19		NM_001374258.1	ENSP00000496776.1
BRAF	ENST00000646891.2	c.504+6092T>C		intron_variant	Intron 3 of 17		NM_004333.6	ENSP00000493543.1

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62617 AN: 151962 Hom.: 18069 Cov.: 32

Gnomad AFR AF: 0.827

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.390

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

GnomAD4 genome AF: 0.412 AC: 62732 AN: 152078 Hom.: 18135 Cov.: 32 AF XY: 0.407 AC XY: 30269 AN XY: 74342

African (AFR) AF: 0.827 AC: 34302 AN: 41478

American (AMR) AF: 0.308 AC: 4714 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 1158 AN: 3468

East Asian (EAS) AF: 0.180 AC: 930 AN: 5178

South Asian (SAS) AF: 0.388 AC: 1875 AN: 4828

European-Finnish (FIN) AF: 0.205 AC: 2169 AN: 10558

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.242 AC: 16445 AN: 67964

Other (OTH) AF: 0.389 AC: 823 AN: 2114

Alfa AF: 0.292 Hom.: 4148

Bravo AF: 0.435

Asia WGS AF: 0.326 AC: 1134 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.3
DANN	Benign	0.56
PhyloP100		-0.062
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1267622; hg19: chr7-140528317;