rs12050217

Positions:

• chr14-96262416-A-G

Variant summary

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

The NM_000710.4(BDKRB1):​c.-129-236A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 152,038 control chromosomes in the GnomAD database, including 3,826 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 0.22 (3826 hom., cov: 31)
• Consequence: BDKRB1 NM_000710.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.111

Genes affected

BDKRB1 (HGNC:1029): (bradykinin receptor B1) Bradykinin, a 9 aa peptide, is generated in pathophysiologic conditions such as inflammation, trauma, burns, shock, and allergy. The protein encoded by this gene belongs to the G-protein coupled receptor 1 family. Two types of G-protein coupled receptors have been found which bind bradykinin and mediate responses to these pathophysiologic conditions. The protein encoded by this gene is one of these receptors and is synthesized de novo following tissue injury. Receptor binding leads to an increase in the cytosolic calcium ion concentration, ultimately resulting in chronic and acute inflammatory responses. [provided by RefSeq, Aug 2020]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BDKRB1	NM_000710.4	c.-129-236A>G		intron_variant		ENST00000216629.11	NP_000701.2
LOC124903375	XR_007064322.1	n.213-2524T>C		intron_variant, non_coding_transcript_variant
BDKRB1	NM_001386007.1	c.-10-1257A>G		intron_variant			NP_001372936.1
LOC124903375	XR_007064323.1	n.196T>C		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BDKRB1	ENST00000216629.11	c.-129-236A>G		intron_variant		1	NM_000710.4	ENSP00000216629	P1
BDKRB1	ENST00000553356.1	c.-129-236A>G		intron_variant		1		ENSP00000452064
	ENST00000553638.1	n.257-2524T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33076 AN: 151920 Hom.: 3824 Cov.: 31

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.242

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

GnomAD4 genome AF: 0.218 AC: 33083 AN: 152038 Hom.: 3826 Cov.: 31 AF XY: 0.218 AC XY: 16196 AN XY: 74294

Gnomad4 AFR AF: 0.183

Gnomad4 AMR AF: 0.310

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.413

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.214

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.241

Alfa AF: 0.209 Hom.: 7326

Bravo AF: 0.227

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.42

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: rs12050217; hg19: chr14-96728753;