19-50835250-C-T

Position:

• chr19-50835250-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000326856.8(KLK15):​c.-32+1865G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 152,046 control chromosomes in the GnomAD database, including 8,502 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 0.31 (8502 hom., cov: 32)
• Consequence: KLK15 ENST00000326856.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.54

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC105372441	NR_131203.1	n.213+3957C>T		intron_variant
LOC105372441	NR_131205.1	n.230+3957C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLK15	ENST00000326856.8	c.-32+1865G>A		intron_variant		5		ENSP00000314783.4
ENSG00000267968	ENST00000598079.1	n.213+3957C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46575 AN: 151928 Hom.: 8483 Cov.: 32

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.323

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

GnomAD4 genome AF: 0.307 AC: 46633 AN: 152046 Hom.: 8502 Cov.: 32 AF XY: 0.305 AC XY: 22687 AN XY: 74334

Gnomad4 AFR AF: 0.509

Gnomad4 AMR AF: 0.233

Gnomad4 ASJ AF: 0.352

Gnomad4 EAS AF: 0.112

Gnomad4 SAS AF: 0.175

Gnomad4 FIN AF: 0.248

Gnomad4 NFE AF: 0.231

Gnomad4 OTH AF: 0.319

Alfa AF: 0.158 Hom.: 341

Bravo AF: 0.318

Asia WGS AF: 0.159 AC: 556 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.29
DANN	Benign	0.37

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs266856; hg19: chr19-51338506;