7-140924774-GGGAGGCGGAGGCGGAGGC-GGGAGGC

Variant names:

• chr7-140924774-GGGAGGCGGAGGC-G
• rs727502907
• NM_001374258.1:c.-83_-72delGCCTCCGCCTCC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_004333.6(BRAF):​c.-83_-72delGCCTCCGCCTCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000985 in 586,848 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0025 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00047 (1 hom.)
• Consequence: BRAF NM_004333.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00

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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00249 (374/150376) while in subpopulation AFR AF= 0.00704 (289/41074). AF 95% confidence interval is 0.00637. There are 0 homozygotes in gnomad4. There are 180 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 374 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRAF	NM_001374258.1	c.-83_-72delGCCTCCGCCTCC		5_prime_UTR_variant	Exon 1 of 20	ENST00000644969.2	NP_001361187.1
BRAF	NM_004333.6	c.-83_-72delGCCTCCGCCTCC		5_prime_UTR_variant	Exon 1 of 18	ENST00000646891.2	NP_004324.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRAF	ENST00000644969.2	c.-83_-72delGCCTCCGCCTCC		5_prime_UTR_variant	Exon 1 of 20		NM_001374258.1	ENSP00000496776.1
BRAF	ENST00000646891.2	c.-83_-72delGCCTCCGCCTCC		5_prime_UTR_variant	Exon 1 of 18		NM_004333.6	ENSP00000493543.1

Frequencies

GnomAD3 genomes AF: 0.00248 AC: 373 AN: 150270 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00706

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00225

Gnomad ASJ AF: 0.00347

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000417

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000475

Gnomad OTH AF: 0.00194

GnomAD4 exome AF: 0.000467 AC: 204 AN: 436472 Hom.: 1 AF XY: 0.000442 AC XY: 105 AN XY: 237424

Gnomad4 AFR exome AF: 0.00470

Gnomad4 AMR exome AF: 0.000715

Gnomad4 ASJ exome AF: 0.00145

Gnomad4 EAS exome AF: 0.000127

Gnomad4 SAS exome AF: 0.000134

Gnomad4 FIN exome AF: 0.000101

Gnomad4 NFE exome AF: 0.000310

Gnomad4 OTH exome AF: 0.00108

GnomAD4 genome AF: 0.00249 AC: 374 AN: 150376 Hom.: 0 Cov.: 30 AF XY: 0.00245 AC XY: 180 AN XY: 73504

Gnomad4 AFR AF: 0.00704

Gnomad4 AMR AF: 0.00225

Gnomad4 ASJ AF: 0.00347

Gnomad4 EAS AF: 0.000197

Gnomad4 SAS AF: 0.000418

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000475

Gnomad4 OTH AF: 0.00192

Alfa AF: 0.0000543 Hom.: 0

Bravo AF: 0.00284

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: rs727502907; hg19: chr7-140624574;