chr14-96238679-C-A

Position:

• chr14-96238679-C-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.86).
• 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BDKRB2	NM_001379692.1	c.74+1498C>A		intron_variant		ENST00000554311.2	NP_001366621.1
BDKRB2	NM_000623.4	c.74+1498C>A		intron_variant			NP_000614.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BDKRB2	ENST00000542454.2	c.-1731C>A		5_prime_UTR_variant	3/3	1		ENSP00000439459.2
BDKRB2	ENST00000554311.2	c.74+1498C>A		intron_variant		1	NM_001379692.1	ENSP00000450482.1
ENSG00000258691	ENST00000553811.1	c.74+1498C>A		intron_variant		2		ENSP00000450984.1
BDKRB2	ENST00000539359.1	c.-173-1017C>A		intron_variant		2		ENSP00000438376.1

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

Gnomad4 AFR exome AF: 0.000325

Gnomad4 AMR exome AF: 0.0359

Gnomad4 ASJ exome AF: 0.00139

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00838

Gnomad4 FIN exome AF: 0.0120

Gnomad4 NFE exome AF: 0.00674

Gnomad4 OTH exome AF: 0.00438

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

Gnomad4 AFR AF: 0.00202

Gnomad4 AMR AF: 0.0193

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.00663

Gnomad4 FIN AF: 0.00405

Gnomad4 NFE AF: 0.00732

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00774 Hom.: 1

Bravo AF: 0.00800

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.8
DANN	Benign	0.85

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: rs2069579; hg19: chr14-96705016;