14-96242495-G-T

Position:

• chr14-96242495-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001379692.1(BDKRB2):​c.*991G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.075 in 152,352 control chromosomes in the GnomAD database, including 568 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 0.075 (568 hom., cov: 34)
  • Exomes 𝑓: 0.083 (0 hom.)
• Consequence: BDKRB2 NM_001379692.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0940

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BDKRB2	NM_001379692.1	c.*991G>T		3_prime_UTR_variant	3/3	ENST00000554311.2	NP_001366621.1
BDKRB2	NM_000623.4	c.*991G>T		3_prime_UTR_variant	3/3		NP_000614.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BDKRB2	ENST00000554311.2	c.*991G>T		3_prime_UTR_variant	3/3	1	NM_001379692.1	ENSP00000450482	P1
BDKRB2	ENST00000542454.2	c.*991G>T		3_prime_UTR_variant	3/3	1		ENSP00000439459

Frequencies

GnomAD3 genomes AF: 0.0750 AC: 11413 AN: 152210 Hom.: 566 Cov.: 34

Gnomad AFR AF: 0.0344

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.0426

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.0557

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.0458

GnomAD4 exome AF: 0.0833 AC: 2 AN: 24 Hom.: 0 Cov.: 0 AF XY: 0.0500 AC XY: 1 AN XY: 20

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.111

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0750 AC: 11424 AN: 152328 Hom.: 568 Cov.: 34 AF XY: 0.0751 AC XY: 5592 AN XY: 74484

Gnomad4 AFR AF: 0.0346

Gnomad4 AMR AF: 0.0425

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.0557

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.0454

Alfa AF: 0.0914 Hom.: 981

Bravo AF: 0.0663

Asia WGS AF: 0.0290 AC: 100 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.2
DANN	Benign	0.76

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: rs2069591; hg19: chr14-96708832;