14-96241886-T-C

Variant names:

• chr14-96241886-T-C
• rs5225
• NM_001379692.1:c.*382T>C

Variant summary

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

The NM_001379692.1(BDKRB2):​c.*382T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0796 in 178,836 control chromosomes in the GnomAD database, including 707 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 0.079 (595 hom., cov: 33)
  • Exomes 𝑓: 0.085 (112 hom.)
• Consequence: BDKRB2 NM_001379692.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.22

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BDKRB2	NM_001379692.1	c.*382T>C		3_prime_UTR_variant	Exon 3 of 3	ENST00000554311.2	NP_001366621.1
BDKRB2	NM_000623.4	c.*382T>C		3_prime_UTR_variant	Exon 3 of 3		NP_000614.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BDKRB2	ENST00000554311.2	c.*382T>C		3_prime_UTR_variant	Exon 3 of 3	1	NM_001379692.1	ENSP00000450482.1
BDKRB2	ENST00000542454.2	c.*382T>C		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000439459.2
ENSG00000258691	ENST00000553811.1	c.74+4705T>C		intron_variant	Intron 2 of 3	2		ENSP00000450984.1

Frequencies

GnomAD3 genomes AF: 0.0786 AC: 11960 AN: 152136 Hom.: 593 Cov.: 33

Gnomad AFR AF: 0.0467

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.0441

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.0568

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.0469

GnomAD4 exome AF: 0.0855 AC: 2272 AN: 26582 Hom.: 112 Cov.: 0 AF XY: 0.0802 AC XY: 1070 AN XY: 13338

Gnomad4 AFR exome AF: 0.0388

Gnomad4 AMR exome AF: 0.0290

Gnomad4 ASJ exome AF: 0.127

Gnomad4 EAS exome AF: 0.000678

Gnomad4 SAS exome AF: 0.0363

Gnomad4 FIN exome AF: 0.108

Gnomad4 NFE exome AF: 0.103

Gnomad4 OTH exome AF: 0.0749

GnomAD4 genome AF: 0.0786 AC: 11972 AN: 152254 Hom.: 595 Cov.: 33 AF XY: 0.0788 AC XY: 5868 AN XY: 74454

Gnomad4 AFR AF: 0.0469

Gnomad4 AMR AF: 0.0440

Gnomad4 ASJ AF: 0.110

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.0568

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.0464

Alfa AF: 0.0872 Hom.: 665

Bravo AF: 0.0708

Asia WGS AF: 0.0290 AC: 101 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.053
DANN	Benign	0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs5225; hg19: chr14-96708223;