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GeneBe

14-96264376-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000710.4(BDKRB1):c.694C>T(p.Arg232Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000725 in 1,614,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000071 ( 0 hom. )

Consequence

BDKRB1
NM_000710.4 missense

Scores

1
6
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0420
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 Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.19922954).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BDKRB1NM_000710.4 linkuse as main transcriptc.694C>T p.Arg232Trp missense_variant 3/3 ENST00000216629.11
LOC124903375XR_007064322.1 linkuse as main transcriptn.212+3993G>A intron_variant, non_coding_transcript_variant
BDKRB1NM_001386007.1 linkuse as main transcriptc.694C>T p.Arg232Trp missense_variant 2/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BDKRB1ENST00000216629.11 linkuse as main transcriptc.694C>T p.Arg232Trp missense_variant 3/31 NM_000710.4 P1
BDKRB1ENST00000553356.1 linkuse as main transcriptc.694C>T p.Arg232Trp missense_variant 3/51
ENST00000553638.1 linkuse as main transcriptn.256+3993G>A intron_variant, non_coding_transcript_variant 2
BDKRB1ENST00000611804.1 linkuse as main transcriptc.694C>T p.Arg232Trp missense_variant 1/1 P1

Frequencies

GnomAD3 genomes
AF:
0.0000854
AC:
13
AN:
152188
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000796
AC:
20
AN:
251388
Hom.:
0
AF XY:
0.0000809
AC XY:
11
AN XY:
135908
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.000199
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000123
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.0000711
AC:
104
AN:
1461880
Hom.:
0
Cov.:
34
AF XY:
0.0000646
AC XY:
47
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.000191
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000800
Gnomad4 OTH exome
AF:
0.000132
GnomAD4 genome
AF:
0.0000854
AC:
13
AN:
152188
Hom.:
0
Cov.:
33
AF XY:
0.0000942
AC XY:
7
AN XY:
74342
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.0000818
Hom.:
0
Bravo
AF:
0.0000567
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000824
AC:
10
EpiCase
AF:
0.000273
EpiControl
AF:
0.000415

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 GeneticsJun 26, 2023The c.694C>T (p.R232W) alteration is located in exon 3 (coding exon 1) of the BDKRB1 gene. This alteration results from a C to T substitution at nucleotide position 694, causing the arginine (R) at amino acid position 232 to be replaced by a tryptophan (W). 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
0.23
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.40
Cadd
Benign
19
Dann
Uncertain
1.0
DEOGEN2
Uncertain
0.60
D;.;D
Eigen
Benign
-0.045
Eigen_PC
Benign
-0.26
FATHMM_MKL
Benign
0.23
N
M_CAP
Uncertain
0.099
D
MetaRNN
Benign
0.20
T;T;T
MetaSVM
Benign
-0.85
T
MutationAssessor
Uncertain
2.7
M;.;M
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.26
T
PROVEAN
Pathogenic
-4.4
D;N;.
REVEL
Benign
0.12
Sift
Uncertain
0.0010
D;D;.
Sift4G
Uncertain
0.0080
D;D;D
Polyphen
1.0
D;D;D
Vest4
0.30
MVP
0.56
MPC
0.11
ClinPred
0.36
T
GERP RS
4.0
Varity_R
0.25
gMVP
0.67

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: rs371690606; hg19: chr14-96730713; COSMIC: COSV53705836; COSMIC: COSV53705836; API