GeneBe

rs373442098

Positions:

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001374258.1(BRAF):​c.2248-10_2248-5del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 27)
Exomes 𝑓: 0.0000013 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

BRAF
NM_001374258.1 splice_region, splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.67
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
BRAFNM_001374258.1 linkuse as main transcriptc.2248-10_2248-5del splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant ENST00000644969.2 NP_001361187.1
BRAFNM_004333.6 linkuse as main transcriptc.2128-10_2128-5del splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant ENST00000646891.2 NP_004324.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
BRAFENST00000644969.2 linkuse as main transcriptc.2248-10_2248-5del splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant NM_001374258.1 ENSP00000496776
BRAFENST00000646891.2 linkuse as main transcriptc.2128-10_2128-5del splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant NM_004333.6 ENSP00000493543 P4

Frequencies

GnomAD3 genomes
Cov.:
27
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000133
AC:
1
AN:
749278
Hom.:
0
AF XY:
0.00000265
AC XY:
1
AN XY:
377318
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000170
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
27

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs373442098; hg19: chr7-140434574; API