chr14-96241886-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001379692.1. 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.*382T>C		3_prime_UTR	Exon 3 of 3	NP_001366621.1
	BDKRB2	NM_000623.4		c.*382T>C		3_prime_UTR	Exon 3 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.*382T>C		3_prime_UTR	Exon 3 of 3	ENSP00000450482.1
	BDKRB2	ENST00000542454.2	TSL:1	c.*382T>C		3_prime_UTR	Exon 3 of 3	ENSP00000439459.2
	ENSG00000258691	ENST00000553811.1	TSL:2	c.74+4705T>C		intron	N/A	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

African (AFR) AF: 0.0388 AC: 37 AN: 954

American (AMR) AF: 0.0290 AC: 65 AN: 2244

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 118 AN: 930

East Asian (EAS) AF: 0.000678 AC: 1 AN: 1476

South Asian (SAS) AF: 0.0363 AC: 27 AN: 744

European-Finnish (FIN) AF: 0.108 AC: 123 AN: 1136

Middle Eastern (MID) AF: 0.0156 AC: 2 AN: 128

European-Non Finnish (NFE) AF: 0.103 AC: 1775 AN: 17314

Other (OTH) AF: 0.0749 AC: 124 AN: 1656

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

African (AFR) AF: 0.0469 AC: 1951 AN: 41560

American (AMR) AF: 0.0440 AC: 673 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 381 AN: 3470

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5182

South Asian (SAS) AF: 0.0568 AC: 274 AN: 4824

European-Finnish (FIN) AF: 0.107 AC: 1137 AN: 10614

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7349 AN: 67990

Other (OTH) AF: 0.0464 AC: 98 AN: 2110

Alfa AF: 0.0863 Hom.: 850

Bravo AF: 0.0708

Asia WGS AF: 0.0290 AC: 101 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.053
DANN	Benign	0.35
PhyloP100		-4.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5225; hg19: chr14-96708223;