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GeneBe

14-96264119-G-A

Variant summary

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

The NM_000710.4(BDKRB1):c.437G>A(p.Arg146Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000182 in 1,595,534 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

BDKRB1
NM_000710.4 missense

Scores

1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.35
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]

Genome browser will be placed here

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=0.103717685).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BDKRB1NM_000710.4 linkuse as main transcriptc.437G>A p.Arg146Gln missense_variant 3/3 ENST00000216629.11
LOC124903375XR_007064322.1 linkuse as main transcriptn.213-4227C>T intron_variant, non_coding_transcript_variant
BDKRB1NM_001386007.1 linkuse as main transcriptc.437G>A p.Arg146Gln missense_variant 2/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BDKRB1ENST00000216629.11 linkuse as main transcriptc.437G>A p.Arg146Gln missense_variant 3/31 NM_000710.4 P1
BDKRB1ENST00000553356.1 linkuse as main transcriptc.437G>A p.Arg146Gln missense_variant 3/51
ENST00000553638.1 linkuse as main transcriptn.257-4227C>T intron_variant, non_coding_transcript_variant 2
BDKRB1ENST00000611804.1 linkuse as main transcriptc.437G>A p.Arg146Gln missense_variant 1/1 P1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152184
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.00633
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000128
AC:
3
AN:
234812
Hom.:
0
AF XY:
0.0000238
AC XY:
3
AN XY:
125824
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 SAS exome
AF:
0.0000386
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000187
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000187
AC:
27
AN:
1443232
Hom.:
0
Cov.:
34
AF XY:
0.0000196
AC XY:
14
AN XY:
715602
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000253
Gnomad4 SAS exome
AF:
0.0000122
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000209
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152302
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74460
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000604
Hom.:
0
Bravo
AF:
0.0000113
ExAC
AF:
0.0000247
AC:
3

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 06, 2022The c.437G>A (p.R146Q) alteration is located in exon 3 (coding exon 1) of the BDKRB1 gene. This alteration results from a G to A substitution at nucleotide position 437, causing the arginine (R) at amino acid position 146 to be replaced by a glutamine (Q). 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
0.099
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.44
Cadd
Benign
19
Dann
Uncertain
1.0
DEOGEN2
Benign
0.15
T;.;T
Eigen
Benign
-0.25
Eigen_PC
Benign
-0.21
FATHMM_MKL
Benign
0.31
N
M_CAP
Benign
0.030
D
MetaRNN
Benign
0.10
T;T;T
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
1.1
L;.;L
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.20
T
PROVEAN
Benign
-0.59
N;N;.
REVEL
Benign
0.17
Sift
Benign
0.33
T;T;.
Sift4G
Benign
0.28
T;T;T
Polyphen
0.59
P;P;P
Vest4
0.072
MutPred
0.51
Loss of methylation at R146 (P = 0.0205);Loss of methylation at R146 (P = 0.0205);Loss of methylation at R146 (P = 0.0205);
MVP
0.67
MPC
0.088
ClinPred
0.17
T
GERP RS
4.0
Varity_R
0.072
gMVP
0.47

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: rs756885188; hg19: chr14-96730456; API