rs62487918

Variant names:

• chr7-140777136-G-A
• rs62487918
• NM_001374258.1:c.1638-48C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-140777136-G-A
• chr7-140777136-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001374258.1(BRAF):​c.1638-48C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0703 in 1,592,052 control chromosomes in the GnomAD database, including 4,469 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.057 (289 hom., cov: 32)
  • Exomes 𝑓: 0.072 (4180 hom.)
• Consequence: BRAF NM_001374258.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0310
• Publications: 8 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

ENSG00000289788 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 7-140777136-G-A is Benign according to our data. Variant chr7-140777136-G-A is described in ClinVar as Benign. ClinVar VariationId is 40378.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRAF	NM_001374258.1	c.1638-48C>T		intron_variant	Intron 13 of 19	ENST00000644969.2	NP_001361187.1
BRAF	NM_004333.6	c.1518-48C>T		intron_variant	Intron 12 of 17	ENST00000646891.2	NP_004324.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRAF	ENST00000644969.2	c.1638-48C>T		intron_variant	Intron 13 of 19		NM_001374258.1	ENSP00000496776.1
BRAF	ENST00000646891.2	c.1518-48C>T		intron_variant	Intron 12 of 17		NM_004333.6	ENSP00000493543.1

Frequencies

GnomAD3 genomes AF: 0.0568 AC: 8625 AN: 151816 Hom.: 288 Cov.: 32

Gnomad AFR AF: 0.0226

Gnomad AMI AF: 0.0374

Gnomad AMR AF: 0.0531

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.0848

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0590

Gnomad MID AF: 0.115

Gnomad NFE AF: 0.0694

Gnomad OTH AF: 0.0610

GnomAD2 exomes AF: 0.0703 AC: 17371 AN: 247080 AF XY: 0.0761

Gnomad AFR exome AF: 0.0203

Gnomad AMR exome AF: 0.0317

Gnomad ASJ exome AF: 0.108

Gnomad EAS exome AF: 0.0959

Gnomad FIN exome AF: 0.0624

Gnomad NFE exome AF: 0.0718

Gnomad OTH exome AF: 0.0717

GnomAD4 exome AF: 0.0718 AC: 103337 AN: 1440134 Hom.: 4180 Cov.: 28 AF XY: 0.0740 AC XY: 53110 AN XY: 717382

African (AFR) AF: 0.0185 AC: 609 AN: 32974

American (AMR) AF: 0.0352 AC: 1562 AN: 44312

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 2775 AN: 25954

East Asian (EAS) AF: 0.0834 AC: 3297 AN: 39538

South Asian (SAS) AF: 0.113 AC: 9691 AN: 85614

European-Finnish (FIN) AF: 0.0592 AC: 3148 AN: 53192

Middle Eastern (MID) AF: 0.124 AC: 704 AN: 5666

European-Non Finnish (NFE) AF: 0.0706 AC: 77134 AN: 1093258

Other (OTH) AF: 0.0741 AC: 4417 AN: 59626

GnomAD4 genome AF: 0.0568 AC: 8624 AN: 151918 Hom.: 289 Cov.: 32 AF XY: 0.0576 AC XY: 4273 AN XY: 74216

African (AFR) AF: 0.0226 AC: 938 AN: 41468

American (AMR) AF: 0.0531 AC: 811 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 360 AN: 3466

East Asian (EAS) AF: 0.0847 AC: 437 AN: 5162

South Asian (SAS) AF: 0.115 AC: 552 AN: 4816

European-Finnish (FIN) AF: 0.0590 AC: 617 AN: 10454

Middle Eastern (MID) AF: 0.111 AC: 32 AN: 288

European-Non Finnish (NFE) AF: 0.0694 AC: 4716 AN: 67970

Other (OTH) AF: 0.0604 AC: 127 AN: 2104

Alfa AF: 0.0677 Hom.: 80

Bravo AF: 0.0531

Asia WGS AF: 0.0930 AC: 325 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	7.6
DANN	Benign	0.83
PhyloP100		-0.031
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: rs62487918; hg19: chr7-140476936; COSMIC: COSV56078557;