Genetic Variant NM_005046.4:c.221+10G>A (chr19-50981757-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
KLK7	NM_005046.4 link	c.221+10G>A	intron_variant	Intron 3 of 5	ENST00000595820.6	NP_005037.1	P49862-1A0A024R4H6B4DHX9
KLK7	NM_139277.2 link	c.221+10G>A	intron_variant	Intron 3 of 5		NP_644806.1	P49862-1A0A024R4H6
KLK7	NM_001243126.1 link	c.200+570G>A	intron_variant	Intron 2 of 4		NP_001230055.1	P49862B4DHX9
KLK7	NM_001207053.2 link	c.5+10G>A	intron_variant	Intron 2 of 4		NP_001193982.1	P49862-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLK7	ENST00000595820.6 link	c.221+10G>A		intron_variant	Intron 3 of 5	1	NM_005046.4	ENSP00000470538.1		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

GnomAD3 exomes

AF:

0.548

AC:

89858

AN:

163938

Hom.:

26424

AF XY:

0.548

AC XY:

47228

AN XY:

86256

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 SAS exome

AF:

0.453

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

Gnomad4 AFR exome

AF:

0.100

Gnomad4 AMR exome

AF:

0.620

Gnomad4 ASJ exome

AF:

0.643

Gnomad4 EAS exome

AF:

0.465

Gnomad4 SAS exome

AF:

0.452

Gnomad4 FIN exome

AF:

0.597

Gnomad4 NFE exome

AF:

0.618

Gnomad4 OTH exome

AF:

0.547

GnomAD4 genome

AF:

0.463

AC:

70311

AN:

151960

Hom.:

19826

Cov.:

AF XY:

0.466

AC XY:

34581

AN XY:

74268

show subpopulations

Gnomad4 AFR

AF:

0.123

Gnomad4 AMR

AF:

0.577

Gnomad4 ASJ

AF:

0.645

Gnomad4 EAS

AF:

0.464

Gnomad4 SAS

AF:

0.452

Gnomad4 FIN

AF:

0.598

Gnomad4 NFE

AF:

0.611

Gnomad4 OTH

AF:

0.463

Alfa

AF:

0.515

Hom.:

8217

Bravo

AF:

0.450

Asia WGS

AF:

0.411

AC:

1428

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

6.4

DANN

Benign

0.76

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over