Variant rs3212852 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_017509.4(KLK15):c.481+5G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0192 in 1,558,560 control chromosomes in the GnomAD database, including 392 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.017 ( 44 hom., cov: 32)

Exomes 𝑓: 0.019 ( 348 hom. )

Consequence

KLK15
NM_017509.4 splice_region, intron

Scores

Splicing: ADA: 0.9547

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.277

Variant links:

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]

KLK15 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0169 (2571/152332) while in subpopulation NFE AF= 0.0232 (1581/68016). AF 95% confidence interval is 0.0223. There are 44 homozygotes in gnomad4. There are 1346 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 44 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLK15	NM_017509.4 link	c.481+5G>A		splice_region_variant, intron_variant	Intron 4 of 5	ENST00000598239.6	NP_059979.2	Q9H2R5-1Q6UBM2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLK15	ENST00000598239.6 link	c.481+5G>A		splice_region_variant, intron_variant	Intron 4 of 5	1	NM_017509.4	ENSP00000469315.1		Q9H2R5-1

Frequencies

GnomAD3 genomes

AF:

0.0169

AC:

2573

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00328

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00896

Gnomad ASJ

AF:

0.0239

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00517

Gnomad FIN

AF:

0.0546

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0232

Gnomad OTH

AF:

0.0143

GnomAD3 exomes

AF:

0.0179

AC:

3738

AN:

208336

Hom.:

AF XY:

0.0183

AC XY:

2021

AN XY:

110520

show subpopulations

Gnomad AFR exome

AF:

0.00367

Gnomad AMR exome

AF:

0.00570

Gnomad ASJ exome

AF:

0.0231

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00500

Gnomad FIN exome

AF:

0.0537

Gnomad NFE exome

AF:

0.0230

Gnomad OTH exome

AF:

0.0161

GnomAD4 exome

AF:

0.0195

AC:

27386

AN:

1406228

Hom.:

348

Cov.:

AF XY:

0.0192

AC XY:

13291

AN XY:

692836

show subpopulations

Gnomad4 AFR exome

AF:

0.00274

Gnomad4 AMR exome

AF:

0.00605

Gnomad4 ASJ exome

AF:

0.0224

Gnomad4 EAS exome

AF:

0.0000255

Gnomad4 SAS exome

AF:

0.00478

Gnomad4 FIN exome

AF:

0.0491

Gnomad4 NFE exome

AF:

0.0210

Gnomad4 OTH exome

AF:

0.0170

GnomAD4 genome

AF:

0.0169

AC:

2571

AN:

152332

Hom.:

Cov.:

AF XY:

0.0181

AC XY:

1346

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.00327

Gnomad4 AMR

AF:

0.00889

Gnomad4 ASJ

AF:

0.0239

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00497

Gnomad4 FIN

AF:

0.0546

Gnomad4 NFE

AF:

0.0232

Gnomad4 OTH

AF:

0.0142

Alfa

AF:

0.0185

Hom.:

Bravo

AF:

0.0122

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.86

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.95

dbscSNV1_RF

Benign

0.66

SpliceAI score (max)

0.59

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.59

Position offset: 5

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over