rs2659056

chr19-50832687-T-Cchr19-50832687-T-G

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLK15	NM_017509.4	c.-32+840A>G		intron_variant		ENST00000598239.6
LOC105372441	NR_131205.1	n.230+1394T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLK15	ENST00000598239.6	c.-32+840A>G		intron_variant		1	NM_017509.4	P4
	ENST00000598079.1	n.213+1394T>C		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.0482

Gnomad4 AMR AF: 0.333

Gnomad4 ASJ AF: 0.240

Gnomad4 EAS AF: 0.398

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.343

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.225

Alfa AF: 0.249 Hom.: 7573

Bravo AF: 0.206

Asia WGS AF: 0.316 AC: 1097 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	6.1
Dann	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2659056; hg19: chr19-51335943;