chr7-140726370-G-A

Position:

• chr7-140726370-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001374258.1(BRAF):​c.*124C>T variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.00259 in 1,498,434 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0023 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (10 hom.)
• Consequence: BRAF NM_001374258.1 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.66

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 7-140726370-G-A is Benign according to our data. Variant chr7-140726370-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2499057.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00231 (351/152276) while in subpopulation AMR AF= 0.00451 (69/15294). AF 95% confidence interval is 0.00366. There are 2 homozygotes in gnomad4. There are 159 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 351 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRAF	NM_001374258.1	c.*124C>T		3_prime_UTR_variant	20/20	ENST00000644969.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRAF	ENST00000644969.2	c.*124C>T		3_prime_UTR_variant	20/20		NM_001374258.1
BRAF	ENST00000496384.7	c.*124C>T		3_prime_UTR_variant	19/19	5		A1
BRAF	ENST00000642875.1	n.1826C>T		non_coding_transcript_exon_variant	15/15
BRAF	ENST00000644120.1	n.2664C>T		non_coding_transcript_exon_variant	17/17

Frequencies

GnomAD3 genomes AF: 0.00231 AC: 351 AN: 152158 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00452

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00283

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00331

Gnomad OTH AF: 0.00288

GnomAD4 exome AF: 0.00262 AC: 3524 AN: 1346158 Hom.: 10 Cov.: 35 AF XY: 0.00261 AC XY: 1724 AN XY: 661626

Gnomad4 AFR exome AF: 0.000336

Gnomad4 AMR exome AF: 0.00206

Gnomad4 ASJ exome AF: 0.000392

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000126

Gnomad4 FIN exome AF: 0.00275

Gnomad4 NFE exome AF: 0.00301

Gnomad4 OTH exome AF: 0.00245

GnomAD4 genome AF: 0.00231 AC: 351 AN: 152276 Hom.: 2 Cov.: 32 AF XY: 0.00214 AC XY: 159 AN XY: 74452

Gnomad4 AFR AF: 0.000361

Gnomad4 AMR AF: 0.00451

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00283

Gnomad4 NFE AF: 0.00331

Gnomad4 OTH AF: 0.00285

Alfa AF: 0.00224 Hom.: 0

Bravo AF: 0.00233

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2023

BRAF: BS1 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	19
DANN	Benign	0.86

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs76749791; hg19: chr7-140426170;