19-50832687-T-C

Variant names:

• chr19-50832687-T-C
• rs2659056
• NM_017509.4:c.-32+840A>G

Variant summary

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

The NM_017509.4(KLK15):​c.-32+840A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 152,130 control chromosomes in the GnomAD database, including 4,529 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 0.22 (4529 hom., cov: 31)
• Consequence: KLK15 NM_017509.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0670
• Publications: 23 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017509.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK15	NM_017509.4	MANE Select	c.-32+840A>G		intron	N/A	NP_059979.2
	KLK15	NM_001277081.2		c.-32+840A>G		intron	N/A	NP_001264010.1	Q9H2R5-5
	KLK15	NM_001277082.2		c.-32+840A>G		intron	N/A	NP_001264011.1	M0R0D7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLK15	ENST00000598239.6	TSL:1 MANE Select	c.-32+840A>G		intron	N/A	ENSP00000469315.1	Q9H2R5-1
	KLK15	ENST00000906215.1		c.-31-1164A>G		intron	N/A	ENSP00000576274.1
	KLK15	ENST00000952480.1		c.-32+412A>G		intron	N/A	ENSP00000622539.1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32863 AN: 152012 Hom.: 4527 Cov.: 31

Gnomad AFR AF: 0.0483

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.216 AC: 32869 AN: 152130 Hom.: 4529 Cov.: 31 AF XY: 0.222 AC XY: 16485 AN XY: 74362

African (AFR) AF: 0.0482 AC: 2003 AN: 41550

American (AMR) AF: 0.333 AC: 5083 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 833 AN: 3468

East Asian (EAS) AF: 0.398 AC: 2054 AN: 5158

South Asian (SAS) AF: 0.197 AC: 951 AN: 4824

European-Finnish (FIN) AF: 0.343 AC: 3629 AN: 10572

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.260 AC: 17637 AN: 67962

Other (OTH) AF: 0.225 AC: 475 AN: 2110

Alfa AF: 0.246 Hom.: 12339

Bravo AF: 0.206

Asia WGS AF: 0.316 AC: 1097 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.1
DANN	Benign	0.69
PhyloP100		-0.067
PromoterAI		-0.044	Neutral
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: rs2659056; hg19: chr19-51335943;