chr14-96242495-G-T

Variant names:

• chr14-96242495-G-T
• rs2069591
• NM_001379692.1:c.*991G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 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 -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 rank	MANE	Protein	UniProt
BDKRB2	NM_001379692.1	c.*991G>T		3_prime_UTR_variant	Exon 3 of 3	ENST00000554311.2	NP_001366621.1
BDKRB2	NM_000623.4	c.*991G>T		3_prime_UTR_variant	Exon 3 of 3		NP_000614.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BDKRB2	ENST00000554311.2	c.*991G>T		3_prime_UTR_variant	Exon 3 of 3	1	NM_001379692.1	ENSP00000450482.1
BDKRB2	ENST00000542454.2	c.*991G>T		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000439459.2
ENSG00000258691	ENST00000553811.1	c.74+5314G>T		intron_variant	Intron 2 of 3	2		ENSP00000450984.1
ENSG00000258691	ENST00000555847.1	n.255+100G>T		intron_variant	Intron 1 of 2	3

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.111 AC: 2 AN: 18

Other (OTH) AF: 0.00 AC: 0 AN: 4

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000037155), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.0346 AC: 1438 AN: 41582

American (AMR) AF: 0.0425 AC: 651 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 379 AN: 3468

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5182

South Asian (SAS) AF: 0.0557 AC: 269 AN: 4826

European-Finnish (FIN) AF: 0.107 AC: 1134 AN: 10612

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7349 AN: 68032

Other (OTH) AF: 0.0454 AC: 96 AN: 2116

Alfa AF: 0.0891 Hom.: 1321

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
PhyloP100		0.094
Mutation Taster		=100/0	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: rs2069591; hg19: chr14-96708832;