rs2069579

Variant names:

• chr14-96238679-C-A
• rs2069579
• ENST00000542454.2:c.-1731C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000542454.2(BDKRB2):​c.-1731C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00656 in 967,850 control chromosomes in the GnomAD database, including 24 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 0.0067 (8 hom., cov: 32)
  • Exomes 𝑓: 0.0065 (16 hom.)
• Consequence: BDKRB2 ENST00000542454.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0110
• Publications: 0 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=-0.86).
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00668 (1018/152334) while in subpopulation AMR AF = 0.0193 (296/15300). AF 95% confidence interval is 0.0175. There are 8 homozygotes in GnomAd4. There are 504 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 8 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000542454.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BDKRB2	NM_001379692.1	MANE Select	c.74+1498C>A		intron	N/A	NP_001366621.1	P30411-1
	BDKRB2	NM_000623.4		c.74+1498C>A		intron	N/A	NP_000614.1	P30411-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BDKRB2	ENST00000542454.2	TSL:1	c.-1731C>A		5_prime_UTR	Exon 3 of 3	ENSP00000439459.2	P30411-2
	BDKRB2	ENST00000554311.2	TSL:1 MANE Select	c.74+1498C>A		intron	N/A	ENSP00000450482.1	P30411-1
	ENSG00000258691	ENST00000553811.1	TSL:2	c.74+1498C>A		intron	N/A	ENSP00000450984.1	G3V318

Frequencies

GnomAD3 genomes AF: 0.00667 AC: 1015 AN: 152216 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.00203

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0191

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.00683

Gnomad FIN AF: 0.00405

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00732

Gnomad OTH AF: 0.00478

GnomAD4 exome AF: 0.00654 AC: 5335 AN: 815516 Hom.: 16 Cov.: 16 AF XY: 0.00652 AC XY: 2462 AN XY: 377450

African (AFR) AF: 0.000325 AC: 5 AN: 15396

American (AMR) AF: 0.0359 AC: 35 AN: 974

Ashkenazi Jewish (ASJ) AF: 0.00139 AC: 7 AN: 5034

East Asian (EAS) AF: 0.00 AC: 0 AN: 3550

South Asian (SAS) AF: 0.00838 AC: 135 AN: 16116

European-Finnish (FIN) AF: 0.0120 AC: 5 AN: 416

Middle Eastern (MID) AF: 0.00316 AC: 5 AN: 1584

European-Non Finnish (NFE) AF: 0.00674 AC: 5026 AN: 745708

Other (OTH) AF: 0.00438 AC: 117 AN: 26738

GnomAD4 genome AF: 0.00668 AC: 1018 AN: 152334 Hom.: 8 Cov.: 32 AF XY: 0.00677 AC XY: 504 AN XY: 74490

African (AFR) AF: 0.00202 AC: 84 AN: 41582

American (AMR) AF: 0.0193 AC: 296 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3470

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5184

South Asian (SAS) AF: 0.00663 AC: 32 AN: 4828

European-Finnish (FIN) AF: 0.00405 AC: 43 AN: 10630

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00732 AC: 498 AN: 68020

Other (OTH) AF: 0.00473 AC: 10 AN: 2114

Alfa AF: 0.00759 Hom.: 2

Bravo AF: 0.00800

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.8
DANN	Benign	0.85
PhyloP100		-0.011
Mutation Taster		=298/2	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: rs2069579; hg19: chr14-96705016;