rs5223

Variant names:

• chr14-96204885-G-T
• rs5223
• NM_001379692.1:c.-114G>T

Variant summary

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

The ENST00000554311.2(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 ENST00000554311.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00900
• Publications: 9 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 (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000554311.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BDKRB2	NM_001379692.1	MANE Select	c.-114G>T		5_prime_UTR	Exon 1 of 3	NP_001366621.1
	BDKRB2	NM_000623.4		c.-109G>T		5_prime_UTR	Exon 1 of 3	NP_000614.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BDKRB2	ENST00000554311.2	TSL:1 MANE Select	c.-114G>T		5_prime_UTR	Exon 1 of 3	ENSP00000450482.1
	BDKRB2	ENST00000542454.2	TSL:1	c.-2882G>T		5_prime_UTR	Exon 1 of 3	ENSP00000439459.2
	ENSG00000258691	ENST00000553811.1	TSL:2	c.-109G>T		5_prime_UTR	Exon 1 of 4	ENSP00000450984.1

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

GnomAD2 exomes AF: 0.208 AC: 8599 AN: 41314 AF XY: 0.207

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 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

African (AFR) AF: 0.117 AC: 410 AN: 3512

American (AMR) AF: 0.139 AC: 1755 AN: 12600

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 1216 AN: 5416

East Asian (EAS) AF: 0.000637 AC: 2 AN: 3142

South Asian (SAS) AF: 0.0763 AC: 3314 AN: 43418

European-Finnish (FIN) AF: 0.213 AC: 2111 AN: 9924

Middle Eastern (MID) AF: 0.251 AC: 523 AN: 2080

European-Non Finnish (NFE) AF: 0.269 AC: 28682 AN: 106768

Other (OTH) AF: 0.216 AC: 1979 AN: 9150

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

African (AFR) AF: 0.121 AC: 5023 AN: 41466

American (AMR) AF: 0.174 AC: 2661 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 753 AN: 3472

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5146

South Asian (SAS) AF: 0.0759 AC: 365 AN: 4812

European-Finnish (FIN) AF: 0.226 AC: 2397 AN: 10586

Middle Eastern (MID) AF: 0.288 AC: 84 AN: 292

European-Non Finnish (NFE) AF: 0.266 AC: 18053 AN: 67830

Other (OTH) AF: 0.209 AC: 440 AN: 2106

Alfa AF: 0.231 Hom.: 891

Bravo AF: 0.195

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	11
DANN	Benign	0.58
PhyloP100		0.0090
PromoterAI		-0.014	Neutral
Mutation Taster		=153/147	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: rs5223; hg19: chr14-96671222; COSMIC: COSV60015967;