14-96237147-C-T

Variant names:

• chr14-96237147-C-T
• rs1046248
• ENST00000542454.2:c.-2729C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000542454.2(BDKRB2):​c.-2729C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0869 in 1,613,312 control chromosomes in the GnomAD database, including 7,004 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.075 (506 hom., cov: 33)
  • Exomes 𝑓: 0.088 (6498 hom.)
• Consequence: BDKRB2 ENST00000542454.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.972
• Publications: 34 publications found

Genes affected

BDKRB2 (HGNC:1030): (bradykinin receptor B2) This gene encodes a receptor for bradykinin. The 9 aa bradykinin peptide elicits many responses including vasodilation, edema, smooth muscle spasm and pain fiber stimulation. Bradykinin is released upon activation by pathophysiologic conditions such as trauma and inflammation, and binds to its kinin receptors, B1 and B2. The B2 receptor associates with G proteins that stimulate a phosphatidylinositol-calcium second messenger system. [provided by RefSeq, Apr 2020]

ENSG00000258691 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0019416511).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0944 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BDKRB2	NM_001379692.1	c.40C>T	p.Arg14Cys	missense_variant	Exon 2 of 3	ENST00000554311.2	NP_001366621.1
BDKRB2	NM_000623.4	c.40C>T	p.Arg14Cys	missense_variant	Exon 2 of 3		NP_000614.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BDKRB2	ENST00000554311.2	c.40C>T	p.Arg14Cys	missense_variant	Exon 2 of 3	1	NM_001379692.1	ENSP00000450482.1
ENSG00000258691	ENST00000553811.1	c.40C>T	p.Arg14Cys	missense_variant	Exon 2 of 4	2		ENSP00000450984.1

Frequencies

GnomAD3 genomes AF: 0.0751 AC: 11419 AN: 152128 Hom.: 505 Cov.: 33

Gnomad AFR AF: 0.0506

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.0570

Gnomad ASJ AF: 0.0516

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0168

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0963

Gnomad OTH AF: 0.0751

GnomAD2 exomes AF: 0.0690 AC: 17347 AN: 251382 AF XY: 0.0688

Gnomad AFR exome AF: 0.0544

Gnomad AMR exome AF: 0.0395

Gnomad ASJ exome AF: 0.0501

Gnomad EAS exome AF: 0.000544

Gnomad FIN exome AF: 0.118

Gnomad NFE exome AF: 0.0970

Gnomad OTH exome AF: 0.0757

GnomAD4 exome AF: 0.0882 AC: 128834 AN: 1461066 Hom.: 6498 Cov.: 31 AF XY: 0.0859 AC XY: 62443 AN XY: 726918

African (AFR) AF: 0.0499 AC: 1671 AN: 33470

American (AMR) AF: 0.0412 AC: 1841 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0507 AC: 1326 AN: 26132

East Asian (EAS) AF: 0.000227 AC: 9 AN: 39700

South Asian (SAS) AF: 0.0188 AC: 1623 AN: 86256

European-Finnish (FIN) AF: 0.115 AC: 6135 AN: 53408

Middle Eastern (MID) AF: 0.0746 AC: 430 AN: 5766

European-Non Finnish (NFE) AF: 0.100 AC: 111419 AN: 1111232

Other (OTH) AF: 0.0725 AC: 4380 AN: 60378

GnomAD4 genome AF: 0.0750 AC: 11420 AN: 152246 Hom.: 506 Cov.: 33 AF XY: 0.0729 AC XY: 5429 AN XY: 74432

African (AFR) AF: 0.0505 AC: 2097 AN: 41556

American (AMR) AF: 0.0569 AC: 870 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0516 AC: 179 AN: 3470

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5184

South Asian (SAS) AF: 0.0170 AC: 82 AN: 4820

European-Finnish (FIN) AF: 0.115 AC: 1223 AN: 10596

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0963 AC: 6553 AN: 68014

Other (OTH) AF: 0.0743 AC: 157 AN: 2112

Alfa AF: 0.0850 Hom.: 1675

Bravo AF: 0.0712

TwinsUK AF: 0.109 AC: 406

ALSPAC AF: 0.105 AC: 405

ESP6500AA AF: 0.0508 AC: 224

ESP6500EA AF: 0.0976 AC: 839

ExAC AF: 0.0689 AC: 8365

Asia WGS AF: 0.0160 AC: 55 AN: 3478

EpiCase AF: 0.0885

EpiControl AF: 0.0987

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	14
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T;.
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.061	N
LIST_S2	Benign	0.56	T;T
MetaRNN	Benign	0.0019	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;.
PhyloP100		0.97
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.28	N;N
REVEL	Benign	0.090
Sift	Benign	0.17	T;D
Sift4G	Benign	0.070	T;D
Polyphen		0.88	P;.
Vest4		0.28
MPC		0.83
ClinPred		0.013	T
GERP RS		1.8
Varity_R		0.084
gMVP		0.29
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1046248; hg19: chr14-96703484; COSMIC: COSV60014195; COSMIC: COSV60014195;