14-96262416-A-G

Variant names:

• chr14-96262416-A-G
• rs12050217
• NM_000710.4:c.-129-236A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

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]

ENSG00000258691 (HGNC:):

BDKRB1-AS1 (HGNC:58458):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000710.4. 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
	BDKRB1	NM_000710.4	MANE Select	c.-129-236A>G		intron	N/A	NP_000701.2
	BDKRB1	NM_001386007.1		c.-10-1257A>G		intron	N/A	NP_001372936.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BDKRB1	ENST00000216629.11	TSL:1 MANE Select	c.-129-236A>G		intron	N/A	ENSP00000216629.6
	BDKRB1	ENST00000553356.1	TSL:1	c.-129-236A>G		intron	N/A	ENSP00000452064.1
	ENSG00000258691	ENST00000553811.1	TSL:2	c.75-236A>G		intron	N/A	ENSP00000450984.1

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

African (AFR) AF: 0.183 AC: 7602 AN: 41470

American (AMR) AF: 0.310 AC: 4737 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 723 AN: 3468

East Asian (EAS) AF: 0.413 AC: 2132 AN: 5160

South Asian (SAS) AF: 0.170 AC: 820 AN: 4812

European-Finnish (FIN) AF: 0.214 AC: 2266 AN: 10572

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.206 AC: 14017 AN: 67970

Other (OTH) AF: 0.241 AC: 509 AN: 2112

Alfa AF: 0.212 Hom.: 16391

Bravo AF: 0.227

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.42
PhyloP100		-0.11
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: rs12050217; hg19: chr14-96728753;