Genetic Variant KLK11:c.-35-197G>A (chr19-51025863-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_001136032.3(KLK11):c.-35-197G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 435,576 control chromosomes in the GnomAD database, including 5,936 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 0.18 ( 3176 hom., cov: 31)

Exomes 𝑓: 0.13 ( 2760 hom. )

Consequence

KLK11
NM_001136032.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.67

Publications

8 publications found

Variant links:

Genes affected

KLK11 (HGNC:6359): (kallikrein related peptidase 11) 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. Alternate splicing and the use of alternate promoters results in multiple transcript variants encoding distinct isoforms which are differentially expressed. [provided by RefSeq, Dec 2016]

KLK11 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=-0.81).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLK11	NM_001136032.3 link	c.-35-197G>A		intron_variant	Intron 1 of 5	ENST00000453757.8	NP_001129504.1	Q9UBX7-1A0A1R3UDR5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLK11	ENST00000453757.8 link	c.-35-197G>A		intron_variant	Intron 1 of 5	1	NM_001136032.3	ENSP00000413958.2		Q9UBX7-1

Frequencies

GnomAD3 genomes

AF:

0.182

AC:

27727

AN:

151986

Hom.:

3164

Cov.:

show subpopulations

Gnomad AFR

AF:

0.327

Gnomad AMI

AF:

0.0439

Gnomad AMR

AF:

0.114

Gnomad ASJ

AF:

0.0821

Gnomad EAS

AF:

0.0422

Gnomad SAS

AF:

0.165

Gnomad FIN

AF:

0.0954

Gnomad MID

AF:

0.105

Gnomad NFE

AF:

0.143

Gnomad OTH

AF:

0.154

GnomAD4 exome

AF:

0.132

AC:

37434

AN:

283472

Hom.:

2760

Cov.:

AF XY:

0.132

AC XY:

19403

AN XY:

146964

show subpopulations

African (AFR)

AF:

0.320

AC:

2340

AN:

7308

American (AMR)

AF:

0.0911

AC:

716

AN:

7856

Ashkenazi Jewish (ASJ)

AF:

0.0782

AC:

770

AN:

9848

East Asian (EAS)

AF:

0.0609

AC:

1332

AN:

21872

South Asian (SAS)

AF:

0.141

AC:

2336

AN:

16600

European-Finnish (FIN)

AF:

0.0901

AC:

2113

AN:

23458

Middle Eastern (MID)

AF:

0.112

AC:

155

AN:

1390

European-Non Finnish (NFE)

AF:

0.142

AC:

25121

AN:

177218

Other (OTH)

AF:

0.142

AC:

2551

AN:

17922

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1507

3014

4520

6027

7534

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

228

342

456

570

<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:

0.183

AC:

27778

AN:

152104

Hom.:

3176

Cov.:

AF XY:

0.178

AC XY:

13220

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.327

AC:

13580

AN:

41472

American (AMR)

AF:

0.114

AC:

1739

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.0821

AC:

285

AN:

3470

East Asian (EAS)

AF:

0.0423

AC:

218

AN:

5158

South Asian (SAS)

AF:

0.164

AC:

793

AN:

4822

European-Finnish (FIN)

AF:

0.0954

AC:

1011

AN:

10598

Middle Eastern (MID)

AF:

0.0959

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.143

AC:

9756

AN:

67992

Other (OTH)

AF:

0.155

AC:

328

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1070

2140

3210

4280

5350

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

288

576

864

1152

1440

<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:

0.153

Hom.:

3670

Bravo

AF:

0.187

Asia WGS

AF:

0.141

AC:

492

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

9.0

(source)

DANN

Benign

0.79

PhyloP100

1.7

PromoterAI

-0.013

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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