rs266854

Variant names:

• chr19-50834562-A-C
• rs266854
• ENST00000326856.8:c.-32+2553T>G

Your query was ambiguous. Multiple possible variants found:

• chr19-50834562-A-C
• chr19-50834562-A-T

Variant summary

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

The ENST00000326856.8(KLK15):​c.-32+2553T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 151,980 control chromosomes in the GnomAD database, including 38,291 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 0.71 (38291 hom., cov: 31)
• Consequence: KLK15 ENST00000326856.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.901
• Publications: 4 publications found

Genes affected

KLK15 (HGNC:20453): (kallikrein related peptidase 15) Kallikreins are a subgroup of serine proteases having diverse physiological functions. Growing evidence suggests that many kallikreins are implicated in carcinogenesis and some have potential as novel cancer and other disease biomarkers. This gene is one of the fifteen kallikrein subfamily members located in a cluster on chromosome 19. In prostate cancer, this gene has increased expression, which indicates its possible use as a diagnostic or prognostic marker for prostate cancer. The gene contains multiple polyadenylation sites and alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]

ENSG00000267968 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105372441	NR_131203.1	n.213+3269A>C		intron_variant	Intron 2 of 2
LOC105372441	NR_131205.1	n.230+3269A>C		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLK15	ENST00000326856.8	c.-32+2553T>G		intron_variant	Intron 1 of 5	5		ENSP00000314783.4
ENSG00000267968	ENST00000598079.1	n.213+3269A>C		intron_variant	Intron 2 of 2	3
KLK15	ENST00000695965.1	c.-1067T>G		upstream_gene_variant				ENSP00000512291.1

Frequencies

GnomAD3 genomes AF: 0.709 AC: 107721 AN: 151862 Hom.: 38254 Cov.: 31

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.803

Gnomad AMR AF: 0.726

Gnomad ASJ AF: 0.819

Gnomad EAS AF: 0.677

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.797

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.716

Gnomad OTH AF: 0.749

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

GnomAD4 genome AF: 0.709 AC: 107804 AN: 151980 Hom.: 38291 Cov.: 31 AF XY: 0.714 AC XY: 53025 AN XY: 74298

African (AFR) AF: 0.669 AC: 27709 AN: 41434

American (AMR) AF: 0.725 AC: 11068 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.819 AC: 2843 AN: 3472

East Asian (EAS) AF: 0.677 AC: 3494 AN: 5160

South Asian (SAS) AF: 0.645 AC: 3107 AN: 4818

European-Finnish (FIN) AF: 0.797 AC: 8413 AN: 10550

Middle Eastern (MID) AF: 0.786 AC: 231 AN: 294

European-Non Finnish (NFE) AF: 0.715 AC: 48626 AN: 67962

Other (OTH) AF: 0.749 AC: 1581 AN: 2110

Alfa AF: 0.724 Hom.: 4971

Bravo AF: 0.701

Asia WGS AF: 0.667 AC: 2323 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.7
DANN	Benign	0.69
PhyloP100		-0.90
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs266854; hg19: chr19-51337818;