Genetic Variant KLK15:n.1149G>A (chr19-50825538-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The ENST00000601680.1(KLK15):n.1149G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0262 in 349,582 control chromosomes in the GnomAD database, including 173 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 0.025 ( 64 hom., cov: 32)

Exomes 𝑓: 0.027 ( 109 hom. )

Consequence

KLK15
ENST00000601680.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.128

Publications

9 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0246 (3742/152228) while in subpopulation NFE AF = 0.0368 (2505/68008). AF 95% confidence interval is 0.0356. There are 64 homozygotes in GnomAd4. There are 1734 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 64 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLK15	NM_017509.4 link	c.*258G>A		3_prime_UTR_variant	Exon 6 of 6	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.*258G>A		3_prime_UTR_variant	Exon 6 of 6	1	NM_017509.4	ENSP00000469315.1		Q9H2R5-1

Frequencies

GnomAD3 genomes

AF:

0.0246

AC:

3741

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00669

Gnomad AMI

AF:

0.0647

Gnomad AMR

AF:

0.0353

Gnomad ASJ

AF:

0.0349

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00560

Gnomad FIN

AF:

0.0127

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0368

Gnomad OTH

AF:

0.0311

GnomAD4 exome

AF:

0.0274

AC:

5404

AN:

197354

Hom.:

109

Cov.:

AF XY:

0.0267

AC XY:

2695

AN XY:

101072

show subpopulations

African (AFR)

AF:

0.00684

AC:

AN:

6436

American (AMR)

AF:

0.0278

AC:

208

AN:

7490

Ashkenazi Jewish (ASJ)

AF:

0.0322

AC:

221

AN:

6872

East Asian (EAS)

AF:

0.00

AC:

AN:

14052

South Asian (SAS)

AF:

0.00525

AC:

AN:

13522

European-Finnish (FIN)

AF:

0.0187

AC:

239

AN:

12802

Middle Eastern (MID)

AF:

0.0325

AC:

AN:

984

European-Non Finnish (NFE)

AF:

0.0345

AC:

4236

AN:

122850

Other (OTH)

AF:

0.0286

AC:

353

AN:

12346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

263

525

788

1050

1313

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0246

AC:

3742

AN:

152228

Hom.:

Cov.:

AF XY:

0.0233

AC XY:

1734

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.00667

AC:

277

AN:

41550

American (AMR)

AF:

0.0353

AC:

540

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0349

AC:

121

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5180

South Asian (SAS)

AF:

0.00581

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.0127

AC:

134

AN:

10592

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0368

AC:

2505

AN:

68008

Other (OTH)

AF:

0.0308

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

201

401

602

802

1003

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

176

220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0333

Hom.:

213

Bravo

AF:

0.0257

Asia WGS

AF:

0.00346

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

7.3

(source)

DANN

Benign

0.79

PhyloP100

-0.13

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over