14-96222430-C-T

Variant names:

• chr14-96222430-C-T
• rs8012552
• NM_001379692.1:c.-39-14639C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001379692.1(BDKRB2):​c.-39-14639C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 151,738 control chromosomes in the GnomAD database, including 22,251 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 0.54 (22251 hom., cov: 31)
• Consequence: BDKRB2 NM_001379692.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.538
• Publications: 12 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.584 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.-39-14639C>T		intron	N/A	NP_001366621.1
	BDKRB2	NM_000623.4		c.-34-14644C>T		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.-39-14639C>T		intron	N/A	ENSP00000450482.1
	BDKRB2	ENST00000542454.2	TSL:1	c.-2807-14639C>T		intron	N/A	ENSP00000439459.2
	ENSG00000258691	ENST00000553811.1	TSL:2	c.-34-14644C>T		intron	N/A	ENSP00000450984.1

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81541 AN: 151618 Hom.: 22249 Cov.: 31

Gnomad AFR AF: 0.453

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.520

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.565

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.589

Gnomad OTH AF: 0.552

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

GnomAD4 genome AF: 0.538 AC: 81565 AN: 151738 Hom.: 22251 Cov.: 31 AF XY: 0.535 AC XY: 39667 AN XY: 74146

African (AFR) AF: 0.453 AC: 18686 AN: 41254

American (AMR) AF: 0.517 AC: 7893 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.550 AC: 1907 AN: 3466

East Asian (EAS) AF: 0.520 AC: 2677 AN: 5150

South Asian (SAS) AF: 0.519 AC: 2489 AN: 4798

European-Finnish (FIN) AF: 0.565 AC: 5959 AN: 10550

Middle Eastern (MID) AF: 0.521 AC: 152 AN: 292

European-Non Finnish (NFE) AF: 0.589 AC: 40025 AN: 67932

Other (OTH) AF: 0.552 AC: 1163 AN: 2108

Alfa AF: 0.575 Hom.: 39050

Bravo AF: 0.533

Asia WGS AF: 0.525 AC: 1830 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.8
DANN	Benign	0.57
PhyloP100		0.54
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: rs8012552; hg19: chr14-96688767;