14-96264610-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_000710.4(BDKRB1):c.928G>C(p.Val310Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000195 in 1,614,186 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00020 (6 hom.)
• Consequence: BDKRB1 NM_000710.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.155

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007072568).
• BP6: Variant 14-96264610-G-C is Benign according to our data. Variant chr14-96264610-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 788119.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BDKRB1	NM_000710.4	c.928G>C	p.Val310Leu	missense_variant	3/3	ENST00000216629.11
LOC124903375	XR_007064322.1	n.212+3759C>G		intron_variant, non_coding_transcript_variant
BDKRB1	NM_001386007.1	c.928G>C	p.Val310Leu	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BDKRB1	ENST00000216629.11	c.928G>C	p.Val310Leu	missense_variant	3/3	1	NM_000710.4	P1
BDKRB1	ENST00000553356.1	c.730G>C	p.Val244Leu	missense_variant	4/5	1
	ENST00000553638.1	n.256+3759C>G		intron_variant, non_coding_transcript_variant		2
BDKRB1	ENST00000611804.1	c.928G>C	p.Val310Leu	missense_variant	1/1			P1

Frequencies

GnomAD3 genomes AF: 0.000184 AC: 28 AN: 152180 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000851

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000445 AC: 112 AN: 251486 Hom.: 0 AF XY: 0.000544 AC XY: 74 AN XY: 135920

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00336

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000196 AC: 286 AN: 1461888 Hom.: 6 Cov.: 33 AF XY: 0.000285 AC XY: 207 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000112

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00305

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000450

Gnomad4 OTH exome AF: 0.000199

GnomAD4 genome AF: 0.000184 AC: 28 AN: 152298 Hom.: 0 Cov.: 33 AF XY: 0.000255 AC XY: 19 AN XY: 74464

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.000849

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00269

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.000117

ExAC AF: 0.000445 AC: 54

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jun 28, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	15
DANN	Benign	0.66
DEOGEN2	Benign	0.056	T;.;T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.16	N
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.0071	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.78	N;.;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.24	N;N;.
REVEL	Benign	0.056
Sift	Benign	0.37	T;T;.
Sift4G	Benign	0.72	T;T;T
Polyphen		0.0080	B;B;B
Vest4		0.055
MutPred		0.48		Gain of sheet (P = 0.1208);.;Gain of sheet (P = 0.1208);
MVP		0.13
MPC		0.11
ClinPred		0.016	T
GERP RS		1.6
Varity_R		0.076
gMVP		0.091

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

Other links and lift over

dbSNP: rs576380894; hg19: chr14-96730947;