rs4900312

Variant names:

• chr14-96212637-A-G
• rs4900312
• NM_001379692.1:c.-40+7678A>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+7678A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.767 in 152,140 control chromosomes in the GnomAD database, including 45,230 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 0.77 (45230 hom., cov: 31)
• Consequence: BDKRB2 NM_001379692.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.20
• Publications: 8 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=-1.1).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.954 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BDKRB2	NM_001379692.1	MANE Select	c.-40+7678A>G		intron	N/A	NP_001366621.1
	BDKRB2	NM_000623.4		c.-35+7678A>G		intron	N/A	NP_000614.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BDKRB2	ENST00000554311.2	TSL:1 MANE Select	c.-40+7678A>G		intron	N/A	ENSP00000450482.1
	BDKRB2	ENST00000542454.2	TSL:1	c.-2808+7678A>G		intron	N/A	ENSP00000439459.2
	ENSG00000258691	ENST00000553811.1	TSL:2	c.-35+7678A>G		intron	N/A	ENSP00000450984.1

Frequencies

GnomAD3 genomes AF: 0.768 AC: 116698 AN: 152022 Hom.: 45214 Cov.: 31

Gnomad AFR AF: 0.690

Gnomad AMI AF: 0.822

Gnomad AMR AF: 0.684

Gnomad ASJ AF: 0.757

Gnomad EAS AF: 0.976

Gnomad SAS AF: 0.832

Gnomad FIN AF: 0.863

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.798

Gnomad OTH AF: 0.774

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

GnomAD4 genome AF: 0.767 AC: 116761 AN: 152140 Hom.: 45230 Cov.: 31 AF XY: 0.770 AC XY: 57231 AN XY: 74370

African (AFR) AF: 0.690 AC: 28610 AN: 41480

American (AMR) AF: 0.684 AC: 10456 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.757 AC: 2625 AN: 3466

East Asian (EAS) AF: 0.976 AC: 5048 AN: 5170

South Asian (SAS) AF: 0.830 AC: 4003 AN: 4820

European-Finnish (FIN) AF: 0.863 AC: 9138 AN: 10594

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.798 AC: 54268 AN: 67996

Other (OTH) AF: 0.775 AC: 1639 AN: 2116

Alfa AF: 0.784 Hom.: 141664

Bravo AF: 0.753

Asia WGS AF: 0.902 AC: 3136 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.19
DANN	Benign	0.23
PhyloP100		-5.2
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: rs4900312; hg19: chr14-96678974;