NM_000710.4:c.342C>G

Variant names:

• chr14-96264024-C-G
• rs142760903
• NM_000710.4:c.342C>G

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_000710.4(BDKRB1):​c.342C>G​(p.Asn114Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00018 in 1,613,984 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00019 (0 hom.)
• Consequence: BDKRB1 NM_000710.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.10
• Publications: 0 publications found

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]

ENSG00000258793 (HGNC:58458):

ENSG00000258691 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.41797668).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000710.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BDKRB1	NM_000710.4	MANE Select	c.342C>G	p.Asn114Lys	missense	Exon 3 of 3	NP_000701.2
	BDKRB1	NM_001386007.1		c.342C>G	p.Asn114Lys	missense	Exon 2 of 2	NP_001372936.1	P46663

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BDKRB1	ENST00000216629.11	TSL:1 MANE Select	c.342C>G	p.Asn114Lys	missense	Exon 3 of 3	ENSP00000216629.6	P46663
	BDKRB1	ENST00000553356.1	TSL:1	c.342C>G	p.Asn114Lys	missense	Exon 3 of 5	ENSP00000452064.1	G3V4Y2
	BDKRB1	ENST00000611804.1	TSL:6	c.342C>G	p.Asn114Lys	missense	Exon 1 of 1	ENSP00000479276.1	P46663

Frequencies

GnomAD3 genomes AF: 0.000112 AC: 17 AN: 152200 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.000147 AC: 37 AN: 251286 AF XY: 0.000133

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.000298

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000370

Gnomad NFE exome AF: 0.000194

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000187 AC: 274 AN: 1461784 Hom.: 0 Cov.: 34 AF XY: 0.000199 AC XY: 145 AN XY: 727190

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000671 AC: 3 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.000191 AC: 5 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86238

European-Finnish (FIN) AF: 0.000337 AC: 18 AN: 53416

Middle Eastern (MID) AF: 0.000694 AC: 4 AN: 5766

European-Non Finnish (NFE) AF: 0.000209 AC: 232 AN: 1111958

Other (OTH) AF: 0.000199 AC: 12 AN: 60390

GnomAD4 genome AF: 0.000112 AC: 17 AN: 152200 Hom.: 0 Cov.: 33 AF XY: 0.000134 AC XY: 10 AN XY: 74350

African (AFR) AF: 0.0000965 AC: 4 AN: 41448

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68036

Other (OTH) AF: 0.000957 AC: 2 AN: 2090

Alfa AF: 0.000251 Hom.: 0

Bravo AF: 0.0000869

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.000148 AC: 18

EpiCase AF: 0.000436

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	1.2
DANN	Benign	0.97
DEOGEN2	Uncertain	0.52	D
Eigen	Benign	-0.74
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		-2.1
PrimateAI	Benign	0.37	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Benign	0.22
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.19	T
Polyphen		1.0	D
Vest4		0.20
MutPred		0.79		Gain of ubiquitination at N114 (P = 0.0192)
MVP		0.28
MPC		0.40
ClinPred		0.34	T
GERP RS		-5.5
PromoterAI		-0.065	Neutral
Varity_R		0.72
gMVP		0.59
Mutation Taster		=79/21	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

Other links and lift over

dbSNP: rs142760903; hg19: chr14-96730361;