Genetic Variant BDKRB2:c.-2729C>T (chr14-96237147-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000542454(BDKRB2):c.-2729C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0869 in 1,613,312 control chromosomes in the GnomAD database, including 7,004 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 ( 506 hom., cov: 33)

Exomes 𝑓: 0.088 ( 6498 hom. )

Consequence

BDKRB2
ENST00000542454 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.972

Variant links:

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]

BDKRB2 links:

ENSG00000258691 (HGNC:):

ENSG00000258691 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019416511).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0944 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BDKRB2	NM_001379692.1 link	c.40C>T	p.Arg14Cys	missense_variant	Exon 2 of 3	ENST00000554311.2	NP_001366621.1
BDKRB2	NM_000623.4 link	c.40C>T	p.Arg14Cys	missense_variant	Exon 2 of 3		NP_000614.1	P30411-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BDKRB2	ENST00000554311.2 link	c.40C>T	p.Arg14Cys	missense_variant	Exon 2 of 3	1	NM_001379692.1	ENSP00000450482.1		P30411-1
ENSG00000258691	ENST00000553811.1 link	c.40C>T	p.Arg14Cys	missense_variant	Exon 2 of 4	2		ENSP00000450984.1		G3V318

Frequencies

GnomAD3 genomes

AF:

0.0751

AC:

11419

AN:

152128

Hom.:

505

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0506

Gnomad AMI

AF:

0.246

Gnomad AMR

AF:

0.0570

Gnomad ASJ

AF:

0.0516

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.0168

Gnomad FIN

AF:

0.115

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0963

Gnomad OTH

AF:

0.0751

GnomAD3 exomes

AF:

0.0690

AC:

17347

AN:

251382

Hom.:

802

AF XY:

0.0688

AC XY:

9346

AN XY:

135856

show subpopulations

Gnomad AFR exome

AF:

0.0544

Gnomad AMR exome

AF:

0.0395

Gnomad ASJ exome

AF:

0.0501

Gnomad EAS exome

AF:

0.000544

Gnomad SAS exome

AF:

0.0177

Gnomad FIN exome

AF:

0.118

Gnomad NFE exome

AF:

0.0970

Gnomad OTH exome

AF:

0.0757

GnomAD4 exome

AF:

0.0882

AC:

128834

AN:

1461066

Hom.:

6498

Cov.:

AF XY:

0.0859

AC XY:

62443

AN XY:

726918

show subpopulations

Gnomad4 AFR exome

AF:

0.0499

Gnomad4 AMR exome

AF:

0.0412

Gnomad4 ASJ exome

AF:

0.0507

Gnomad4 EAS exome

AF:

0.000227

Gnomad4 SAS exome

AF:

0.0188

Gnomad4 FIN exome

AF:

0.115

Gnomad4 NFE exome

AF:

0.100

Gnomad4 OTH exome

AF:

0.0725

GnomAD4 genome

AF:

0.0750

AC:

11420

AN:

152246

Hom.:

506

Cov.:

AF XY:

0.0729

AC XY:

5429

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0505

Gnomad4 AMR

AF:

0.0569

Gnomad4 ASJ

AF:

0.0516

Gnomad4 EAS

AF:

0.00154

Gnomad4 SAS

AF:

0.0170

Gnomad4 FIN

AF:

0.115

Gnomad4 NFE

AF:

0.0963

Gnomad4 OTH

AF:

0.0743

Alfa

AF:

0.0878

Hom.:

1328

Bravo

AF:

0.0712

TwinsUK

AF:

0.109

AC:

406

ALSPAC

AF:

0.105

AC:

405

ESP6500AA

AF:

0.0508

AC:

224

ESP6500EA

AF:

0.0976

AC:

839

ExAC

AF:

0.0689

AC:

8365

Asia WGS

AF:

0.0160

AC:

AN:

3478

EpiCase

AF:

0.0885

EpiControl

AF:

0.0987

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;.

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.061

LIST_S2

Benign

0.56

T;T

MetaRNN

Benign

0.0019

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

N;.

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.28

N;N

REVEL

Benign

0.090

Sift

Benign

0.17

T;D

Sift4G

Benign

0.070

T;D

Polyphen

0.88

P;.

Vest4

0.28

MPC

0.83

ClinPred

0.013

GERP RS

1.8

Varity_R

0.084

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over