19-50834452-T-C

Variant names:

• chr19-50834452-T-C
• rs266853
• ENST00000326856.8:c.-32+2663A>G

Variant summary

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

The ENST00000326856.8(KLK15):​c.-32+2663A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 151,604 control chromosomes in the GnomAD database, including 3,825 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 (3825 hom., cov: 29)
• Consequence: KLK15 ENST00000326856.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0410
• Publications: 4 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105372441	NR_131203.1	n.213+3159T>C		intron_variant	Intron 2 of 2
LOC105372441	NR_131205.1	n.230+3159T>C		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLK15	ENST00000326856.8	c.-32+2663A>G		intron_variant	Intron 1 of 5	5		ENSP00000314783.4
ENSG00000267968	ENST00000598079.1	n.213+3159T>C		intron_variant	Intron 2 of 2	3
KLK15	ENST00000695965.1	c.-957A>G		upstream_gene_variant				ENSP00000512291.1

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33383 AN: 151484 Hom.: 3827 Cov.: 29

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.253

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

GnomAD4 genome AF: 0.220 AC: 33394 AN: 151604 Hom.: 3825 Cov.: 29 AF XY: 0.219 AC XY: 16221 AN XY: 74064

African (AFR) AF: 0.245 AC: 10114 AN: 41310

American (AMR) AF: 0.197 AC: 3003 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.326 AC: 1127 AN: 3460

East Asian (EAS) AF: 0.112 AC: 576 AN: 5150

South Asian (SAS) AF: 0.175 AC: 839 AN: 4786

European-Finnish (FIN) AF: 0.196 AC: 2056 AN: 10492

Middle Eastern (MID) AF: 0.243 AC: 71 AN: 292

European-Non Finnish (NFE) AF: 0.219 AC: 14859 AN: 67872

Other (OTH) AF: 0.249 AC: 526 AN: 2110

Alfa AF: 0.216 Hom.: 462

Bravo AF: 0.224

Asia WGS AF: 0.138 AC: 483 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	5.0
DANN	Benign	0.47
PhyloP100		-0.041
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: rs266853; hg19: chr19-51337708;