14-96264024-C-G

Position:

chr14-96264024-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_000710.4(BDKRB1):c.342C>G(p.Asn114Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00018 in 1,613,984 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

BDKRB1
NM_000710.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.10

Variant links:

Genes affected

BDKRB1 (HGNC:1029): (bradykinin receptor B1) Bradykinin, a 9 aa peptide, is generated in pathophysiologic conditions such as inflammation, trauma, burns, shock, and allergy. The protein encoded by this gene belongs to the G-protein coupled receptor 1 family. Two types of G-protein coupled receptors have been found which bind bradykinin and mediate responses to these pathophysiologic conditions. The protein encoded by this gene is one of these receptors and is synthesized de novo following tissue injury. Receptor binding leads to an increase in the cytosolic calcium ion concentration, ultimately resulting in chronic and acute inflammatory responses. [provided by RefSeq, Aug 2020]

BDKRB1 links:

ENSG00000258793 (HGNC:):

ENSG00000258793 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.41797668).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BDKRB1	NM_000710.4 linkuse as main transcript	c.342C>G	p.Asn114Lys	missense_variant	3/3	ENST00000216629.11	NP_000701.2	P46663
BDKRB1	NM_001386007.1 linkuse as main transcript	c.342C>G	p.Asn114Lys	missense_variant	2/2		NP_001372936.1
LOC124903375	XR_007064322.1 linkuse as main transcript	n.213-4132G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
BDKRB1	ENST00000216629.11 linkuse as main transcript	c.342C>G	p.Asn114Lys	missense_variant	3/3	1	NM_000710.4	ENSP00000216629.6	P46663
BDKRB1	ENST00000553356.1 linkuse as main transcript	c.342C>G	p.Asn114Lys	missense_variant	3/5	1		ENSP00000452064.1	G3V4Y2
BDKRB1	ENST00000611804.1 linkuse as main transcript	c.342C>G	p.Asn114Lys	missense_variant	1/1	6		ENSP00000479276.1	P46663
ENSG00000258793	ENST00000553638.1 linkuse as main transcript	n.257-4132G>C		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000147

AC:

AN:

251286

Hom.:

AF XY:

0.000133

AC XY:

AN XY:

135818

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000370

Gnomad NFE exome

AF:

0.000194

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000187

AC:

274

AN:

1461784

Hom.:

Cov.:

AF XY:

0.000199

AC XY:

145

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.000191

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000337

Gnomad4 NFE exome

AF:

0.000209

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.000112

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.000957

Alfa

AF:

0.000251

Hom.:

Bravo

AF:

0.0000869

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000148

AC:

EpiCase

AF:

0.000436

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 19, 2022

The c.342C>G (p.N114K) alteration is located in exon 3 (coding exon 1) of the BDKRB1 gene. This alteration results from a C to G substitution at nucleotide position 342, causing the asparagine (N) at amino acid position 114 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.43

CADD

Benign

1.2

DANN

Benign

0.97

DEOGEN2

Uncertain

0.52

D;.;D

Eigen

Benign

-0.74

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.72

.;T;T

M_CAP

Benign

0.043

MetaRNN

Benign

0.42

T;T;T

MetaSVM

Benign

-0.77

MutationAssessor

Pathogenic

3.1

M;.;M

PrimateAI

Benign

0.37

PROVEAN

Pathogenic

-4.5

D;D;.

REVEL

Benign

0.22

Sift

Uncertain

0.0040

D;D;.

Sift4G

Benign

0.19

T;T;T

Polyphen

1.0

D;D;D

Vest4

0.20

MutPred

0.79

Gain of ubiquitination at N114 (P = 0.0192);Gain of ubiquitination at N114 (P = 0.0192);Gain of ubiquitination at N114 (P = 0.0192);

MVP

0.28

MPC

0.40

ClinPred

0.34

GERP RS

-5.5

Varity_R

0.72

gMVP

0.59

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over