chr14-96264133-C-T

Variant names:

• chr14-96264133-C-T
• rs202055275
• NM_000710.4:c.451C>T

Variant summary

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

The NM_000710.4(BDKRB1):​c.451C>T​(p.Arg151Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000539 in 1,594,556 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 0.000072 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000052 (0 hom.)
• Consequence: BDKRB1 NM_000710.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.382
• 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=0.38147393).

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.451C>T	p.Arg151Trp	missense	Exon 3 of 3	NP_000701.2
	BDKRB1	NM_001386007.1		c.451C>T	p.Arg151Trp	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.451C>T	p.Arg151Trp	missense	Exon 3 of 3	ENSP00000216629.6	P46663
	BDKRB1	ENST00000553356.1	TSL:1	c.451C>T	p.Arg151Trp	missense	Exon 3 of 5	ENSP00000452064.1	G3V4Y2
	BDKRB1	ENST00000611804.1	TSL:6	c.451C>T	p.Arg151Trp	missense	Exon 1 of 1	ENSP00000479276.1	P46663

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152200 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000392

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000598 AC: 14 AN: 234202 AF XY: 0.0000558

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000598

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000383

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000282

Gnomad OTH exome AF: 0.000176

GnomAD4 exome AF: 0.0000520 AC: 75 AN: 1442356 Hom.: 0 Cov.: 34 AF XY: 0.0000462 AC XY: 33 AN XY: 715028

African (AFR) AF: 0.00 AC: 0 AN: 33172

American (AMR) AF: 0.0000229 AC: 1 AN: 43608

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24514

East Asian (EAS) AF: 0.000379 AC: 15 AN: 39546

South Asian (SAS) AF: 0.0000244 AC: 2 AN: 82026

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5660

European-Non Finnish (NFE) AF: 0.0000508 AC: 56 AN: 1101848

Other (OTH) AF: 0.0000168 AC: 1 AN: 59582

GnomAD4 genome AF: 0.0000723 AC: 11 AN: 152200 Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6 AN XY: 74358

African (AFR) AF: 0.0000241 AC: 1 AN: 41446

American (AMR) AF: 0.000392 AC: 6 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

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: 0.0000441 AC: 3 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000982

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.0000577 AC: 7

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	Benign	0.17
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T
Eigen	Benign	0.083
Eigen_PC	Benign	-0.091
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.71	T
M_CAP	Pathogenic	0.33	D
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.51	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		0.38
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-2.5	D
REVEL	Uncertain	0.38
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.019	D
Polyphen		1.0	D
Vest4		0.38
MutPred		0.57		Loss of disorder (P = 0.0043)
MVP		0.74
MPC		0.15
ClinPred		0.19	T
GERP RS		3.0
PromoterAI		-0.022	Neutral
Varity_R		0.29
gMVP		0.65
Mutation Taster		=96/4	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: rs202055275; hg19: chr14-96730470;