rs4905474

Positions:

• chr14-96231027-G-A

Variant summary

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

The NM_001379692.1(BDKRB2):​c.-39-6042G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 152,064 control chromosomes in the GnomAD database, including 4,627 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 0.24 (4627 hom., cov: 33)
• Consequence: BDKRB2 NM_001379692.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.82

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BDKRB2	NM_001379692.1	c.-39-6042G>A		intron_variant		ENST00000554311.2
BDKRB2	NM_000623.4	c.-34-6047G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BDKRB2	ENST00000554311.2	c.-39-6042G>A		intron_variant		1	NM_001379692.1	P1
BDKRB2	ENST00000542454.2	c.-2807-6042G>A		intron_variant		1
BDKRB2	ENST00000539359.1	c.-281-6047G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36714 AN: 151946 Hom.: 4617 Cov.: 33

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.283

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.236

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

GnomAD4 genome AF: 0.242 AC: 36760 AN: 152064 Hom.: 4627 Cov.: 33 AF XY: 0.245 AC XY: 18201 AN XY: 74328

Gnomad4 AFR AF: 0.272

Gnomad4 AMR AF: 0.299

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.378

Gnomad4 SAS AF: 0.331

Gnomad4 FIN AF: 0.205

Gnomad4 NFE AF: 0.203

Gnomad4 OTH AF: 0.241

Alfa AF: 0.220 Hom.: 1821

Bravo AF: 0.252

Asia WGS AF: 0.331 AC: 1152 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.013
DANN	Benign	0.17

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: rs4905474; hg19: chr14-96697364;