14-96209596-A-G

Variant names:

• chr14-96209596-A-G
• rs8016905
• NM_001379692.1:c.-40+4637A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001379692.1(BDKRB2):​c.-40+4637A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.672 in 152,118 control chromosomes in the GnomAD database, including 34,735 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 0.67 (34735 hom., cov: 32)
• Consequence: BDKRB2 NM_001379692.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.332
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.707 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BDKRB2	NM_001379692.1	MANE Select	c.-40+4637A>G		intron	N/A	NP_001366621.1	P30411-1
	BDKRB2	NM_000623.4		c.-35+4637A>G		intron	N/A	NP_000614.1	P30411-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BDKRB2	ENST00000554311.2	TSL:1 MANE Select	c.-40+4637A>G		intron	N/A	ENSP00000450482.1	P30411-1
	BDKRB2	ENST00000542454.2	TSL:1	c.-2808+4637A>G		intron	N/A	ENSP00000439459.2	P30411-2
	ENSG00000258691	ENST00000553811.1	TSL:2	c.-35+4637A>G		intron	N/A	ENSP00000450984.1	G3V318

Frequencies

GnomAD3 genomes AF: 0.673 AC: 102225 AN: 152000 Hom.: 34721 Cov.: 32

Gnomad AFR AF: 0.606

Gnomad AMI AF: 0.664

Gnomad AMR AF: 0.613

Gnomad ASJ AF: 0.652

Gnomad EAS AF: 0.676

Gnomad SAS AF: 0.673

Gnomad FIN AF: 0.766

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.713

Gnomad OTH AF: 0.690

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

GnomAD4 genome AF: 0.672 AC: 102290 AN: 152118 Hom.: 34735 Cov.: 32 AF XY: 0.672 AC XY: 49991 AN XY: 74338

African (AFR) AF: 0.606 AC: 25126 AN: 41490

American (AMR) AF: 0.613 AC: 9376 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.652 AC: 2261 AN: 3470

East Asian (EAS) AF: 0.677 AC: 3506 AN: 5182

South Asian (SAS) AF: 0.671 AC: 3226 AN: 4808

European-Finnish (FIN) AF: 0.766 AC: 8099 AN: 10580

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.713 AC: 48442 AN: 67976

Other (OTH) AF: 0.690 AC: 1458 AN: 2114

Alfa AF: 0.696 Hom.: 120954

Bravo AF: 0.660

Asia WGS AF: 0.676 AC: 2352 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.7
DANN	Benign	0.73
PhyloP100		0.33
Mutation Taster		=100/0	polymorphism (auto)

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: rs8016905; hg19: chr14-96675933;