14-96235578-C-T

Position:

• chr14-96235578-C-T

Variant summary

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

The NM_001379692.1(BDKRB2):​c.-39-1491C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0949 in 152,102 control chromosomes in the GnomAD database, including 765 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 0.095 (765 hom., cov: 32)
• Consequence: BDKRB2 NM_001379692.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BDKRB2	NM_001379692.1	c.-39-1491C>T		intron_variant		ENST00000554311.2
BDKRB2	NM_000623.4	c.-34-1496C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BDKRB2	ENST00000554311.2	c.-39-1491C>T		intron_variant		1	NM_001379692.1	P1
BDKRB2	ENST00000542454.2	c.-2807-1491C>T		intron_variant		1
BDKRB2	ENST00000539359.1	c.-281-1496C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0948 AC: 14412 AN: 151984 Hom.: 763 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.0568

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.0819

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0916

Gnomad OTH AF: 0.0905

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

GnomAD4 genome AF: 0.0949 AC: 14430 AN: 152102 Hom.: 765 Cov.: 32 AF XY: 0.0927 AC XY: 6894 AN XY: 74364

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.0566

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.0819

Gnomad4 NFE AF: 0.0916

Gnomad4 OTH AF: 0.0886

Alfa AF: 0.0846 Hom.: 418

Bravo AF: 0.0924

Asia WGS AF: 0.0560 AC: 195 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.2
DANN	Benign	0.45

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: rs2069571; hg19: chr14-96701915;