14-96204802-C-T

Position:

• chr14-96204802-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000542454.2(BDKRB2):​c.-2965C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 358,202 control chromosomes in the GnomAD database, including 29,485 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 0.39 (12013 hom., cov: 32)
  • Exomes 𝑓: 0.40 (17472 hom.)
• Consequence: BDKRB2 ENST00000542454.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0110

Genes affected

BDKRB2 (HGNC:1030): (bradykinin receptor B2) This gene encodes a receptor for bradykinin. The 9 aa bradykinin peptide elicits many responses including vasodilation, edema, smooth muscle spasm and pain fiber stimulation. Bradykinin is released upon activation by pathophysiologic conditions such as trauma and inflammation, and binds to its kinin receptors, B1 and B2. The B2 receptor associates with G proteins that stimulate a phosphatidylinositol-calcium second messenger system. [provided by RefSeq, Apr 2020]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BDKRB2	NM_001379692.1			upstream_gene_variant		ENST00000554311.2	NP_001366621.1
BDKRB2	NM_000623.4			upstream_gene_variant			NP_000614.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BDKRB2	ENST00000542454.2	c.-2965C>T		5_prime_UTR_variant	1/3	1		ENSP00000439459
BDKRB2	ENST00000554311.2			upstream_gene_variant		1	NM_001379692.1	ENSP00000450482	P1
BDKRB2	ENST00000539359.1			upstream_gene_variant		2		ENSP00000438376

Frequencies

GnomAD3 genomes AF: 0.395 AC: 59964 AN: 151932 Hom.: 12014 Cov.: 32

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.406

GnomAD3 exomes AF: 0.407 AC: 25415 AN: 62492 Hom.: 5361 AF XY: 0.402 AC XY: 13790 AN XY: 34304

Gnomad AFR exome AF: 0.289

Gnomad AMR exome AF: 0.436

Gnomad ASJ exome AF: 0.383

Gnomad EAS exome AF: 0.485

Gnomad SAS exome AF: 0.361

Gnomad FIN exome AF: 0.399

Gnomad NFE exome AF: 0.419

Gnomad OTH exome AF: 0.403

GnomAD4 exome AF: 0.405 AC: 83401 AN: 206152 Hom.: 17472 Cov.: 0 AF XY: 0.401 AC XY: 47951 AN XY: 119664

Gnomad4 AFR exome AF: 0.297

Gnomad4 AMR exome AF: 0.439

Gnomad4 ASJ exome AF: 0.391

Gnomad4 EAS exome AF: 0.462

Gnomad4 SAS exome AF: 0.363

Gnomad4 FIN exome AF: 0.398

Gnomad4 NFE exome AF: 0.420

Gnomad4 OTH exome AF: 0.412

GnomAD4 genome AF: 0.395 AC: 59989 AN: 152050 Hom.: 12013 Cov.: 32 AF XY: 0.395 AC XY: 29338 AN XY: 74344

Gnomad4 AFR AF: 0.314

Gnomad4 AMR AF: 0.439

Gnomad4 ASJ AF: 0.385

Gnomad4 EAS AF: 0.497

Gnomad4 SAS AF: 0.394

Gnomad4 FIN AF: 0.404

Gnomad4 NFE AF: 0.425

Gnomad4 OTH AF: 0.403

Alfa AF: 0.413 Hom.: 8744

Bravo AF: 0.398

Asia WGS AF: 0.449 AC: 1563 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	17
DANN	Benign	0.92

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

Publications

LitVar

Other links and lift over

dbSNP: rs1799722; hg19: chr14-96671139; COSMIC: COSV60014910; COSMIC: COSV60014910;