Genetic Variant KLK7:c.221+10G>A (chr19-50981757-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_005046.4(KLK7):c.221+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.576 in 1,535,950 control chromosomes in the GnomAD database, including 268,371 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 0.46 ( 19826 hom., cov: 34)

Exomes 𝑓: 0.59 ( 248545 hom. )

Consequence

KLK7
NM_005046.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.839

Publications

8 publications found

Variant links:

Genes affected

KLK7 (HGNC:6368): (kallikrein related peptidase 7) This gene encodes a member of the kallikrein subfamily of serine proteases. These enzymes have diverse physiological functions and many kallikrein genes are biomarkers for cancer. The encoded protein has chymotrypsin-like activity and plays a role in the proteolysis of intercellular cohesive structures that precedes desquamation, the shedding of the outermost layer of the epidermis. The encoded protein may play a role in cancer invasion and metastasis, and increased expression of this gene is associated with unfavorable prognosis and progression of several types of cancer. Polymorphisms in this gene may play a role in the development of atopic dermatitis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, which is one of fifteen kallikrein subfamily members located in a gene cluster on chromosome 19. [provided by RefSeq, May 2011]

KLK7 links:

ENSG00000267879 (HGNC:):

ENSG00000267879 links:

Genome browser will be placed here

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=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005046.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KLK7	NM_005046.4	MANE Select	c.221+10G>A	intron	N/A	NP_005037.1	P49862-1
KLK7	NM_139277.2		c.221+10G>A	intron	N/A	NP_644806.1	P49862-1
KLK7	NM_001243126.1		c.200+570G>A	intron	N/A	NP_001230055.1	P49862

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KLK7	ENST00000595820.6	TSL:1 MANE Select	c.221+10G>A	intron	N/A	ENSP00000470538.1	P49862-1
KLK7	ENST00000597707.5	TSL:1	c.5+10G>A	intron	N/A	ENSP00000469950.1	P49862-2
KLK7	ENST00000391807.5	TSL:5	c.221+10G>A	intron	N/A	ENSP00000375683.1	P49862-1

Frequencies

GnomAD3 genomes

AF:

0.463

AC:

70305

AN:

151842

Hom.:

19831

Cov.:

show subpopulations

Gnomad AFR

AF:

0.123

Gnomad AMI

AF:

0.781

Gnomad AMR

AF:

0.577

Gnomad ASJ

AF:

0.645

Gnomad EAS

AF:

0.464

Gnomad SAS

AF:

0.451

Gnomad FIN

AF:

0.598

Gnomad MID

AF:

0.456

Gnomad NFE

AF:

0.611

Gnomad OTH

AF:

0.466

GnomAD2 exomes

AF:

0.548

AC:

89858

AN:

163938

AF XY:

0.548

show subpopulations

Gnomad AFR exome

AF:

0.102

Gnomad AMR exome

AF:

0.630

Gnomad ASJ exome

AF:

0.647

Gnomad EAS exome

AF:

0.469

Gnomad FIN exome

AF:

0.594

Gnomad NFE exome

AF:

0.611

Gnomad OTH exome

AF:

0.565

GnomAD4 exome

AF:

0.589

AC:

814882

AN:

1383990

Hom.:

248545

Cov.:

AF XY:

0.586

AC XY:

400153

AN XY:

683128

show subpopulations

African (AFR)

AF:

0.100

AC:

3248

AN:

32372

American (AMR)

AF:

0.620

AC:

21186

AN:

34174

Ashkenazi Jewish (ASJ)

AF:

0.643

AC:

15628

AN:

24304

East Asian (EAS)

AF:

0.465

AC:

17249

AN:

37112

South Asian (SAS)

AF:

0.452

AC:

35132

AN:

77734

European-Finnish (FIN)

AF:

0.597

AC:

29379

AN:

49230

Middle Eastern (MID)

AF:

0.482

AC:

2527

AN:

5246

European-Non Finnish (NFE)

AF:

0.618

AC:

659093

AN:

1066346

Other (OTH)

AF:

0.547

AC:

31440

AN:

57472

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

15118

30236

45355

60473

75591

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17574

35148

52722

70296

87870

<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:

0.463

AC:

70311

AN:

151960

Hom.:

19826

Cov.:

AF XY:

0.466

AC XY:

34581

AN XY:

74268

show subpopulations

African (AFR)

AF:

0.123

AC:

5093

AN:

41490

American (AMR)

AF:

0.577

AC:

8815

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.645

AC:

2236

AN:

3468

East Asian (EAS)

AF:

0.464

AC:

2385

AN:

5144

South Asian (SAS)

AF:

0.452

AC:

2177

AN:

4818

European-Finnish (FIN)

AF:

0.598

AC:

6320

AN:

10574

Middle Eastern (MID)

AF:

0.463

AC:

136

AN:

294

European-Non Finnish (NFE)

AF:

0.611

AC:

41465

AN:

67872

Other (OTH)

AF:

0.463

AC:

975

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1611

3222

4832

6443

8054

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

612

1224

1836

2448

3060

<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:

0.504

Hom.:

8540

Bravo

AF:

0.450

Asia WGS

AF:

0.411

AC:

1428

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

6.4

(source)

DANN

Benign

0.76

PhyloP100

0.84

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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