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GeneBe

14-96263894-T-C

Variant summary

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

The NM_000710.4(BDKRB1):c.212T>C(p.Val71Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000223 in 1,614,120 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 (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

BDKRB1
NM_000710.4 missense

Scores

4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.769
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=0.12180245).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BDKRB1NM_000710.4 linkuse as main transcriptc.212T>C p.Val71Ala missense_variant 3/3 ENST00000216629.11
LOC124903375XR_007064322.1 linkuse as main transcriptn.213-4002A>G intron_variant, non_coding_transcript_variant
BDKRB1NM_001386007.1 linkuse as main transcriptc.212T>C p.Val71Ala missense_variant 2/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BDKRB1ENST00000216629.11 linkuse as main transcriptc.212T>C p.Val71Ala missense_variant 3/31 NM_000710.4 P1
BDKRB1ENST00000553356.1 linkuse as main transcriptc.212T>C p.Val71Ala missense_variant 3/51
ENST00000553638.1 linkuse as main transcriptn.257-4002A>G intron_variant, non_coding_transcript_variant 2
BDKRB1ENST00000611804.1 linkuse as main transcriptc.212T>C p.Val71Ala missense_variant 1/1 P1

Frequencies

GnomAD3 genomes
AF:
0.000145
AC:
22
AN:
152248
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000530
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.00
GnomAD3 exomes
AF:
0.0000358
AC:
9
AN:
251440
Hom.:
0
AF XY:
0.0000368
AC XY:
5
AN XY:
135894
show subpopulations
Gnomad AFR exome
AF:
0.000308
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000958
AC:
14
AN:
1461872
Hom.:
0
Cov.:
34
AF XY:
0.0000110
AC XY:
8
AN XY:
727238
show subpopulations
Gnomad4 AFR exome
AF:
0.000209
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000828
GnomAD4 genome
AF:
0.000145
AC:
22
AN:
152248
Hom.:
0
Cov.:
33
AF XY:
0.000134
AC XY:
10
AN XY:
74388
show subpopulations
Gnomad4 AFR
AF:
0.000530
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000132
Hom.:
0
Bravo
AF:
0.000144
ESP6500AA
AF:
0.000908
AC:
4
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000330
AC:
4
EpiCase
AF:
0.00
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 GeneticsNov 16, 2021The c.212T>C (p.V71A) alteration is located in exon 3 (coding exon 1) of the BDKRB1 gene. This alteration results from a T to C substitution at nucleotide position 212, causing the valine (V) at amino acid position 71 to be replaced by an alanine (A). 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
0.18
BayesDel_addAF
Benign
-0.54
T
BayesDel_noAF
Benign
-0.64
Cadd
Benign
19
Dann
Benign
0.96
DEOGEN2
Uncertain
0.54
D;.;D
Eigen
Benign
-0.27
Eigen_PC
Benign
-0.39
FATHMM_MKL
Uncertain
0.83
D
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.12
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.1
M;.;M
MutationTaster
Benign
0.94
N;N
PrimateAI
Benign
0.30
T
PROVEAN
Uncertain
-3.8
D;D;.
REVEL
Benign
0.11
Sift
Benign
0.042
D;D;.
Sift4G
Benign
0.12
T;T;T
Polyphen
0.53
P;P;P
Vest4
0.038
MVP
0.37
MPC
0.085
ClinPred
0.37
T
GERP RS
0.31
Varity_R
0.26
gMVP
0.39

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: rs148328792; hg19: chr14-96730231; API