14-96264109-A-G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_000710.4(BDKRB1):c.427A>G(p.Met143Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000213 in 1,598,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

BDKRB1
NM_000710.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.198

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13538697).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BDKRB1	NM_000710.4 link	c.427A>G	p.Met143Val	missense_variant	Exon 3 of 3	ENST00000216629.11	NP_000701.2	P46663
BDKRB1	NM_001386007.1 link	c.427A>G	p.Met143Val	missense_variant	Exon 2 of 2		NP_001372936.1
LOC124903375	XR_007064322.1 link	n.213-4217T>C		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BDKRB1	ENST00000216629.11 link	c.427A>G	p.Met143Val	missense_variant	Exon 3 of 3	1	NM_000710.4	ENSP00000216629.6		P46663
ENSG00000258691	ENST00000553811.1 link	c.*402A>G		downstream_gene_variant		2		ENSP00000450984.1		G3V318

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.00000845

AC:

AN:

236816

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000929

Gnomad OTH exome

AF:

0.000173

GnomAD4 exome

AF:

0.0000104

AC:

AN:

1446022

Hom.:

Cov.:

AF XY:

0.00000976

AC XY:

AN XY:

717458

show subpopulations

Gnomad4 AFR exome

AF:

0.00

AC:

AN:

33254

Gnomad4 AMR exome

AF:

0.0000228

AC:

AN:

43822

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

24742

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

39586

Gnomad4 SAS exome

AF:

0.00

AC:

AN:

82642

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

52622

Gnomad4 NFE exome

AF:

0.00000453

AC:

AN:

1103894

Gnomad4 Remaining exome

AF:

0.000151

AC:

AN:

59784

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000125

AC:

AN:

152138

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.00

AC:

AN:

Gnomad4 AMR

AF:

0.00118

AC:

0.00117801

AN:

0.00117801

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.00

AC:

AN:

Gnomad4 OTH

AF:

0.000478

AC:

0.000478011

AN:

0.000478011

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000247

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 15, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.427A>G (p.M143V) alteration is located in exon 3 (coding exon 1) of the BDKRB1 gene. This alteration results from a A to G substitution at nucleotide position 427, causing the methionine (M) at amino acid position 143 to be replaced by a valine (V). 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

Benign

0.078

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.47

CADD

Benign

4.5

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.46

T;.;T

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.60

.;T;T

M_CAP

Benign

0.026

MetaRNN

Benign

0.14

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.66

N;.;N

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-2.9

D;D;.

REVEL

Benign

0.15

Sift

Benign

0.041

D;D;.

Sift4G

Benign

0.14

T;T;T

Polyphen

0.15

B;P;B

Vest4

0.082

MutPred

0.71

Loss of catalytic residue at M143 (P = 0.0154);Loss of catalytic residue at M143 (P = 0.0154);Loss of catalytic residue at M143 (P = 0.0154);

MVP

0.20

MPC

0.069

ClinPred

0.32

GERP RS

4.1

Varity_R

0.23

gMVP

0.50

Mutation Taster

=72/28

polymorphism

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