19-50835128-A-G

Variant names:

• chr19-50835128-A-G
• rs266855
• ENST00000326856.8:c.-32+1987T>C

Variant summary

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

The ENST00000326856.8(KLK15):​c.-32+1987T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.732 in 152,078 control chromosomes in the GnomAD database, including 40,821 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 0.73 (40821 hom., cov: 30)
• Consequence: KLK15 ENST00000326856.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.215
• Publications: 6 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000326856.8. 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
	LOC105372441	NR_131203.1		n.213+3835A>G		intron	N/A
	LOC105372441	NR_131205.1		n.230+3835A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK15	ENST00000326856.8	TSL:5	c.-32+1987T>C		intron	N/A	ENSP00000314783.4
	ENSG00000267968	ENST00000598079.1	TSL:3	n.213+3835A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.732 AC: 111284 AN: 151960 Hom.: 40785 Cov.: 30

Gnomad AFR AF: 0.749

Gnomad AMI AF: 0.803

Gnomad AMR AF: 0.735

Gnomad ASJ AF: 0.818

Gnomad EAS AF: 0.675

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.797

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.716

Gnomad OTH AF: 0.766

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

GnomAD4 genome AF: 0.732 AC: 111364 AN: 152078 Hom.: 40821 Cov.: 30 AF XY: 0.736 AC XY: 54677 AN XY: 74326

African (AFR) AF: 0.749 AC: 31060 AN: 41480

American (AMR) AF: 0.734 AC: 11220 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.818 AC: 2837 AN: 3470

East Asian (EAS) AF: 0.676 AC: 3478 AN: 5148

South Asian (SAS) AF: 0.644 AC: 3105 AN: 4818

European-Finnish (FIN) AF: 0.797 AC: 8425 AN: 10574

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.716 AC: 48658 AN: 67990

Other (OTH) AF: 0.766 AC: 1614 AN: 2108

Alfa AF: 0.714 Hom.: 18458

Bravo AF: 0.729

Asia WGS AF: 0.673 AC: 2344 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.5
DANN	Benign	0.82
PhyloP100		0.21
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: rs266855; hg19: chr19-51338384;