Genetic Variant KLK15:c.*316G>A (chr19-50825480-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_017509.4(KLK15):c.*316G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 194,208 control chromosomes in the GnomAD database, including 6,240 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 ( 4693 hom., cov: 31)

Exomes 𝑓: 0.25 ( 1547 hom. )

Consequence

KLK15
NM_017509.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.324

Publications

12 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=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017509.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
KLK15	NM_017509.4	MANE Select	c.*316G>A	3_prime_UTR	Exon 6 of 6	NP_059979.2
KLK15	NM_001277081.2		c.*316G>A	3_prime_UTR	Exon 6 of 6	NP_001264010.1
KLK15	NM_001277082.2		c.*464G>A	3_prime_UTR	Exon 5 of 5	NP_001264011.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
KLK15	ENST00000598239.6	TSL:1 MANE Select	c.*316G>A	3_prime_UTR	Exon 6 of 6	ENSP00000469315.1
KLK15	ENST00000601680.1	TSL:1	n.1207G>A	non_coding_transcript_exon	Exon 4 of 4
KLK15	ENST00000906215.1		c.*316G>A	3_prime_UTR	Exon 6 of 6	ENSP00000576274.1

Frequencies

GnomAD3 genomes

AF:

0.221

AC:

33557

AN:

151830

Hom.:

4671

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0836

Gnomad AMI

AF:

0.180

Gnomad AMR

AF:

0.352

Gnomad ASJ

AF:

0.232

Gnomad EAS

AF:

0.528

Gnomad SAS

AF:

0.265

Gnomad FIN

AF:

0.291

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.238

Gnomad OTH

AF:

0.212

GnomAD4 exome

AF:

0.252

AC:

10670

AN:

42258

Hom.:

1547

Cov.:

AF XY:

0.253

AC XY:

5371

AN XY:

21266

show subpopulations

African (AFR)

AF:

0.0825

AC:

130

AN:

1576

American (AMR)

AF:

0.407

AC:

678

AN:

1664

Ashkenazi Jewish (ASJ)

AF:

0.216

AC:

367

AN:

1696

East Asian (EAS)

AF:

0.439

AC:

1293

AN:

2948

South Asian (SAS)

AF:

0.244

AC:

291

AN:

1192

European-Finnish (FIN)

AF:

0.287

AC:

691

AN:

2406

Middle Eastern (MID)

AF:

0.127

AC:

AN:

244

European-Non Finnish (NFE)

AF:

0.234

AC:

6469

AN:

27636

Other (OTH)

AF:

0.249

AC:

720

AN:

2896

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

398

795

1193

1590

1988

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

180

240

300

<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:

0.221

AC:

33605

AN:

151950

Hom.:

4693

Cov.:

AF XY:

0.227

AC XY:

16877

AN XY:

74246

show subpopulations

African (AFR)

AF:

0.0836

AC:

3465

AN:

41450

American (AMR)

AF:

0.353

AC:

5387

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.232

AC:

805

AN:

3468

East Asian (EAS)

AF:

0.528

AC:

2720

AN:

5148

South Asian (SAS)

AF:

0.265

AC:

1272

AN:

4800

European-Finnish (FIN)

AF:

0.291

AC:

3073

AN:

10546

Middle Eastern (MID)

AF:

0.133

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.239

AC:

16213

AN:

67974

Other (OTH)

AF:

0.222

AC:

467

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1256

2511

3767

5022

6278

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

364

728

1092

1456

1820

<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:

0.222

Hom.:

5360

Bravo

AF:

0.222

Asia WGS

AF:

0.397

AC:

1376

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.6

(source)

DANN

Benign

0.86

PhyloP100

-0.32

Mutation Taster

=100/0

polymorphism (auto)

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over