ENST00000326856.8:c.-32+1164G>A

Variant names:

• chr19-50835951-C-T
• rs2033496
• ENST00000326856.8:c.-32+1164G>A

Variant summary

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

The ENST00000326856.8(KLK15):​c.-32+1164G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 152,124 control chromosomes in the GnomAD database, including 18,091 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 0.48 (18091 hom., cov: 33)
• Consequence: KLK15 ENST00000326856.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0840
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105372441	NR_131203.1	n.213+4658C>T		intron_variant	Intron 2 of 2
LOC105372441	NR_131205.1	n.230+4658C>T		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLK15	ENST00000326856.8	c.-32+1164G>A		intron_variant	Intron 1 of 5	5		ENSP00000314783.4
ENSG00000267968	ENST00000598079.1	n.213+4658C>T		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72774 AN: 152002 Hom.: 18062 Cov.: 33

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.640

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.490

Gnomad EAS AF: 0.272

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.488

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

GnomAD4 genome AF: 0.479 AC: 72840 AN: 152124 Hom.: 18091 Cov.: 33 AF XY: 0.480 AC XY: 35717 AN XY: 74360

African (AFR) AF: 0.594 AC: 24639 AN: 41488

American (AMR) AF: 0.369 AC: 5645 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.490 AC: 1701 AN: 3472

East Asian (EAS) AF: 0.272 AC: 1408 AN: 5168

South Asian (SAS) AF: 0.410 AC: 1975 AN: 4818

European-Finnish (FIN) AF: 0.500 AC: 5300 AN: 10592

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.448 AC: 30434 AN: 67976

Other (OTH) AF: 0.481 AC: 1017 AN: 2116

Alfa AF: 0.452 Hom.: 24273

Bravo AF: 0.476

Asia WGS AF: 0.336 AC: 1174 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.3
DANN	Benign	0.83
PhyloP100		0.084
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: rs2033496; hg19: chr19-51339207; COSMIC: COSV56831529; COSMIC: COSV56831529;