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GeneBe

14-96264266-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000710.4(BDKRB1):c.584A>G(p.His195Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000527 in 1,614,122 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H195N) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000053 ( 0 hom. )

Consequence

BDKRB1
NM_000710.4 missense

Scores

2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.162
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06671575).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BDKRB1NM_000710.4 linkuse as main transcriptc.584A>G p.His195Arg missense_variant 3/3 ENST00000216629.11
LOC124903375XR_007064322.1 linkuse as main transcriptn.212+4103T>C intron_variant, non_coding_transcript_variant
BDKRB1NM_001386007.1 linkuse as main transcriptc.584A>G p.His195Arg missense_variant 2/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BDKRB1ENST00000216629.11 linkuse as main transcriptc.584A>G p.His195Arg missense_variant 3/31 NM_000710.4 P1
BDKRB1ENST00000553356.1 linkuse as main transcriptc.584A>G p.His195Arg missense_variant 3/51
ENST00000553638.1 linkuse as main transcriptn.256+4103T>C intron_variant, non_coding_transcript_variant 2
BDKRB1ENST00000611804.1 linkuse as main transcriptc.584A>G p.His195Arg missense_variant 1/1 P1

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152112
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.000866
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000123
AC:
31
AN:
251462
Hom.:
0
AF XY:
0.000103
AC XY:
14
AN XY:
135914
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.000376
Gnomad ASJ exome
AF:
0.000595
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000703
Gnomad OTH exome
AF:
0.000489
GnomAD4 exome
AF:
0.0000534
AC:
78
AN:
1461892
Hom.:
0
Cov.:
34
AF XY:
0.0000481
AC XY:
35
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.000380
Gnomad4 ASJ exome
AF:
0.000803
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000207
Gnomad4 OTH exome
AF:
0.000149
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152230
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74452
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.000866
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000987
Hom.:
0
Bravo
AF:
0.0000756
ExAC
AF:
0.000157
AC:
19
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

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 submitterclinical testingAmbry GeneticsJan 07, 2022The c.584A>G (p.H195R) 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 584, causing the histidine (H) at amino acid position 195 to be replaced by an arginine (R). 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
0.087
BayesDel_addAF
Benign
-0.43
T
BayesDel_noAF
Benign
-0.56
Cadd
Benign
9.7
Dann
Benign
0.95
DEOGEN2
Benign
0.22
T;.;T
Eigen
Benign
-0.51
Eigen_PC
Benign
-0.67
FATHMM_MKL
Benign
0.15
N
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.067
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.3
M;.;M
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.31
T
PROVEAN
Uncertain
-2.6
D;D;.
REVEL
Benign
0.11
Sift
Benign
0.057
T;T;.
Sift4G
Benign
0.39
T;T;T
Polyphen
0.85
P;P;P
Vest4
0.22
MutPred
0.53
Gain of solvent accessibility (P = 0.1133);Gain of solvent accessibility (P = 0.1133);Gain of solvent accessibility (P = 0.1133);
MVP
0.44
MPC
0.24
ClinPred
0.14
T
GERP RS
1.3
Varity_R
0.089
gMVP
0.28

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.

Other links and lift over

dbSNP: rs566659692; hg19: chr14-96730603; API