14-96219959-G-C

Position:

• chr14-96219959-G-C

Variant summary

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

The NM_001379692.1(BDKRB2):​c.-40+15000G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 151,834 control chromosomes in the GnomAD database, including 7,075 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 0.29 (7075 hom., cov: 31)
• Consequence: BDKRB2 NM_001379692.1 intron
• 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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BDKRB2	NM_001379692.1	c.-40+15000G>C		intron_variant		ENST00000554311.2
BDKRB2	NM_000623.4	c.-35+15000G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BDKRB2	ENST00000554311.2	c.-40+15000G>C		intron_variant		1	NM_001379692.1	P1
BDKRB2	ENST00000542454.2	c.-2808+15000G>C		intron_variant		1
BDKRB2	ENST00000539359.1	c.-282+15000G>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43908 AN: 151714 Hom.: 7076 Cov.: 31

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.342

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.289 AC: 43903 AN: 151834 Hom.: 7075 Cov.: 31 AF XY: 0.284 AC XY: 21036 AN XY: 74182

Gnomad4 AFR AF: 0.155

Gnomad4 AMR AF: 0.287

Gnomad4 ASJ AF: 0.371

Gnomad4 EAS AF: 0.242

Gnomad4 SAS AF: 0.256

Gnomad4 FIN AF: 0.271

Gnomad4 NFE AF: 0.373

Gnomad4 OTH AF: 0.341

Alfa AF: 0.206 Hom.: 514

Bravo AF: 0.289

Asia WGS AF: 0.236 AC: 828 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.2
DANN	Benign	0.44

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: rs11847625; hg19: chr14-96686296;