rs5223

Positions:

• chr14-96204885-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001379692.1(BDKRB2):​c.-114G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 347,906 control chromosomes in the GnomAD database, including 8,493 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 0.20 (3426 hom., cov: 32)
  • Exomes 𝑓: 0.20 (5067 hom.)
• Consequence: BDKRB2 NM_001379692.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00900

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BDKRB2	NM_001379692.1	c.-114G>T		5_prime_UTR_variant	1/3	ENST00000554311.2	NP_001366621.1
BDKRB2	NM_000623.4	c.-109G>T		5_prime_UTR_variant	1/3		NP_000614.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BDKRB2	ENST00000554311.2	c.-114G>T		5_prime_UTR_variant	1/3	1	NM_001379692.1	ENSP00000450482	P1
BDKRB2	ENST00000542454.2	c.-2882G>T		5_prime_UTR_variant	1/3	1		ENSP00000439459
BDKRB2	ENST00000539359.1	c.-356G>T		5_prime_UTR_variant	1/4	2		ENSP00000438376

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30072 AN: 151778 Hom.: 3422 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.00155

Gnomad SAS AF: 0.0756

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.274

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.212

GnomAD3 exomes AF: 0.208 AC: 8599 AN: 41314 Hom.: 1097 AF XY: 0.207 AC XY: 4651 AN XY: 22442

Gnomad AFR exome AF: 0.119

Gnomad AMR exome AF: 0.161

Gnomad ASJ exome AF: 0.244

Gnomad EAS exome AF: 0.000575

Gnomad SAS exome AF: 0.0864

Gnomad FIN exome AF: 0.258

Gnomad NFE exome AF: 0.296

Gnomad OTH exome AF: 0.257

GnomAD4 exome AF: 0.204 AC: 39992 AN: 196010 Hom.: 5067 Cov.: 0 AF XY: 0.191 AC XY: 21732 AN XY: 113544

Gnomad4 AFR exome AF: 0.117

Gnomad4 AMR exome AF: 0.139

Gnomad4 ASJ exome AF: 0.225

Gnomad4 EAS exome AF: 0.000637

Gnomad4 SAS exome AF: 0.0763

Gnomad4 FIN exome AF: 0.213

Gnomad4 NFE exome AF: 0.269

Gnomad4 OTH exome AF: 0.216

GnomAD4 genome AF: 0.198 AC: 30080 AN: 151896 Hom.: 3426 Cov.: 32 AF XY: 0.193 AC XY: 14356 AN XY: 74290

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.00155

Gnomad4 SAS AF: 0.0759

Gnomad4 FIN AF: 0.226

Gnomad4 NFE AF: 0.266

Gnomad4 OTH AF: 0.209

Alfa AF: 0.231 Hom.: 891

Bravo AF: 0.195

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	11
DANN	Benign	0.58

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: rs5223; hg19: chr14-96671222; COSMIC: COSV60015967;