rs199739317

Variant names:

• chr14-96240403-C-G
• rs199739317
• NM_001379692.1:c.75C>G

Your query was ambiguous. Multiple possible variants found:

• chr14-96240403-C-G
• chr14-96240403-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001379692.1(BDKRB2):​c.75C>G​(p.Ser25Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000156 in 1,282,422 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 19/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S25S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: BDKRB2 NM_001379692.1 missense, splice_region
• Scores: Splicing: ADA: 0.00004452
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.203
• Publications: 1 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14796802).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BDKRB2	NM_001379692.1	c.75C>G	p.Ser25Arg	missense_variant, splice_region_variant	Exon 3 of 3	ENST00000554311.2	NP_001366621.1
BDKRB2	NM_000623.4	c.75C>G	p.Ser25Arg	missense_variant, splice_region_variant	Exon 3 of 3		NP_000614.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BDKRB2	ENST00000554311.2	c.75C>G	p.Ser25Arg	missense_variant, splice_region_variant	Exon 3 of 3	1	NM_001379692.1	ENSP00000450482.1
ENSG00000258691	ENST00000553811.1	c.74+3222C>G		intron_variant	Intron 2 of 3	2		ENSP00000450984.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000659 AC: 1 AN: 151718 AF XY: 0.0000124

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000128

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000156 AC: 2 AN: 1282422 Hom.: 0 Cov.: 30 AF XY: 0.00000161 AC XY: 1 AN XY: 622198

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 28098

American (AMR) AF: 0.00 AC: 0 AN: 22110

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18084

East Asian (EAS) AF: 0.00 AC: 0 AN: 34750

South Asian (SAS) AF: 0.00 AC: 0 AN: 52378

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46946

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5046

European-Non Finnish (NFE) AF: 0.00000196 AC: 2 AN: 1022816

Other (OTH) AF: 0.00 AC: 0 AN: 52194

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000770867), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000860 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	1.7
DANN	Benign	0.88
DEOGEN2	Benign	0.34	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.46	N
PhyloP100		-0.20
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.17
Sift	Benign	0.097	T
Sift4G	Benign	0.48	T
Polyphen		0.47	P
Vest4		0.30
MutPred		0.40		Gain of methylation at S25 (P = 0.028);
MVP		0.67
ClinPred		0.050	T
GERP RS		0.30
Varity_R		0.050
gMVP		0.45
Mutation Taster		=84/16	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000045
dbscSNV1_RF	Benign	0.13
SpliceAI score (max)		0.030		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: rs199739317; hg19: chr14-96706740;