Genetic Variant NM_017509.4:c.-31-111G>A (chr19-50831634-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.-31-111G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 559,944 control chromosomes in the GnomAD database, including 19,953 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 0.27 ( 5752 hom., cov: 30)

Exomes 𝑓: 0.26 ( 14201 hom. )

Consequence

KLK15
NM_017509.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.207

Publications

16 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:

ENSG00000267968 (HGNC:):

ENSG00000267968 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=-0.89).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLK15	NM_017509.4 link	c.-31-111G>A		intron_variant	Intron 1 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.-31-111G>A		intron_variant	Intron 1 of 5	1	NM_017509.4	ENSP00000469315.1		Q9H2R5-1

Frequencies

GnomAD3 genomes

AF:

0.273

AC:

41407

AN:

151800

Hom.:

5737

Cov.:

show subpopulations

Gnomad AFR

AF:

0.320

Gnomad AMI

AF:

0.189

Gnomad AMR

AF:

0.264

Gnomad ASJ

AF:

0.167

Gnomad EAS

AF:

0.316

Gnomad SAS

AF:

0.337

Gnomad FIN

AF:

0.192

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.259

Gnomad OTH

AF:

0.233

GnomAD4 exome

AF:

0.256

AC:

104529

AN:

408026

Hom.:

14201

AF XY:

0.258

AC XY:

53492

AN XY:

207452

show subpopulations

African (AFR)

AF:

0.316

AC:

2819

AN:

8930

American (AMR)

AF:

0.294

AC:

2185

AN:

7434

Ashkenazi Jewish (ASJ)

AF:

0.170

AC:

1904

AN:

11210

East Asian (EAS)

AF:

0.304

AC:

6957

AN:

22862

South Asian (SAS)

AF:

0.327

AC:

6455

AN:

19716

European-Finnish (FIN)

AF:

0.212

AC:

7242

AN:

34182

Middle Eastern (MID)

AF:

0.174

AC:

466

AN:

2678

European-Non Finnish (NFE)

AF:

0.254

AC:

70802

AN:

278758

Other (OTH)

AF:

0.256

AC:

5699

AN:

22256

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

3621

7242

10863

14484

18105

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1194

2388

3582

4776

5970

<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:

0.273

AC:

41452

AN:

151918

Hom.:

5752

Cov.:

AF XY:

0.269

AC XY:

19988

AN XY:

74262

show subpopulations

African (AFR)

AF:

0.320

AC:

13244

AN:

41426

American (AMR)

AF:

0.265

AC:

4044

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.167

AC:

579

AN:

3470

East Asian (EAS)

AF:

0.316

AC:

1625

AN:

5146

South Asian (SAS)

AF:

0.338

AC:

1626

AN:

4816

European-Finnish (FIN)

AF:

0.192

AC:

2031

AN:

10576

Middle Eastern (MID)

AF:

0.187

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.259

AC:

17585

AN:

67902

Other (OTH)

AF:

0.233

AC:

491

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1495

2989

4484

5978

7473

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

450

900

1350

1800

2250

<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:

0.264

Hom.:

20859

Bravo

AF:

0.281

Asia WGS

AF:

0.324

AC:

1122

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

3.2

(source)

DANN

Benign

0.60

PhyloP100

0.21

PromoterAI

0.0012

Neutral

(source)

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over