14-96204802-C-T

Variant names:

• chr14-96204802-C-T
• rs1799722
• ENST00000542454.2:c.-2965C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 57 publications found

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]

ENSG00000258691 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
BDKRB2	NM_001379692.1	c.-197C>T		upstream_gene_variant		ENST00000554311.2	NP_001366621.1
BDKRB2	NM_000623.4	c.-192C>T		upstream_gene_variant			NP_000614.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BDKRB2	ENST00000542454.2	c.-2965C>T		5_prime_UTR_variant	Exon 1 of 3	1		ENSP00000439459.2
BDKRB2	ENST00000554311.2	c.-197C>T		upstream_gene_variant		1	NM_001379692.1	ENSP00000450482.1
ENSG00000258691	ENST00000553811.1	c.-192C>T		upstream_gene_variant		2		ENSP00000450984.1
BDKRB2	ENST00000539359.1	c.-439C>T		upstream_gene_variant		2		ENSP00000438376.1

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

GnomAD2 exomes AF: 0.407 AC: 25415 AN: 62492 AF XY: 0.402

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 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

African (AFR) AF: 0.297 AC: 1234 AN: 4154

American (AMR) AF: 0.439 AC: 7685 AN: 17514

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 2653 AN: 6786

East Asian (EAS) AF: 0.462 AC: 1097 AN: 2376

South Asian (SAS) AF: 0.363 AC: 16644 AN: 45842

European-Finnish (FIN) AF: 0.398 AC: 4052 AN: 10186

Middle Eastern (MID) AF: 0.406 AC: 949 AN: 2338

European-Non Finnish (NFE) AF: 0.420 AC: 45117 AN: 107328

Other (OTH) AF: 0.412 AC: 3970 AN: 9628

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

African (AFR) AF: 0.314 AC: 13023 AN: 41496

American (AMR) AF: 0.439 AC: 6704 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 1333 AN: 3466

East Asian (EAS) AF: 0.497 AC: 2556 AN: 5146

South Asian (SAS) AF: 0.394 AC: 1901 AN: 4820

European-Finnish (FIN) AF: 0.404 AC: 4279 AN: 10586

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.425 AC: 28884 AN: 67948

Other (OTH) AF: 0.403 AC: 849 AN: 2108

Alfa AF: 0.415 Hom.: 11707

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
PhyloP100		-0.011
PromoterAI		0.014	Neutral
Mutation Taster		=300/0	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: rs1799722; hg19: chr14-96671139; COSMIC: COSV60014910; COSMIC: COSV60014910;