14-96209596-A-G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BDKRB2	NM_001379692.1	c.-40+4637A>G		intron_variant	Intron 1 of 2	ENST00000554311.2	NP_001366621.1
BDKRB2	NM_000623.4	c.-35+4637A>G		intron_variant	Intron 1 of 2		NP_000614.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BDKRB2	ENST00000554311.2	c.-40+4637A>G		intron_variant	Intron 1 of 2	1	NM_001379692.1	ENSP00000450482.1
BDKRB2	ENST00000542454.2	c.-2808+4637A>G		intron_variant	Intron 1 of 2	1		ENSP00000439459.2
ENSG00000258691	ENST00000553811.1	c.-35+4637A>G		intron_variant	Intron 1 of 3	2		ENSP00000450984.1
BDKRB2	ENST00000539359.1	c.-282+4637A>G		intron_variant	Intron 1 of 3	2		ENSP00000438376.1

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

Gnomad4 AFR AF: 0.606

Gnomad4 AMR AF: 0.613

Gnomad4 ASJ AF: 0.652

Gnomad4 EAS AF: 0.677

Gnomad4 SAS AF: 0.671

Gnomad4 FIN AF: 0.766

Gnomad4 NFE AF: 0.713

Gnomad4 OTH AF: 0.690

Alfa AF: 0.702 Hom.: 52956

Bravo AF: 0.660

Asia WGS AF: 0.676 AC: 2352 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.7
DANN	Benign	0.73

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: rs8016905; hg19: chr14-96675933;