Variant 19-50910650-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004917.5(KLK4):c.61+28T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 1,547,322 control chromosomes in the GnomAD database, including 55,780 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 9489 hom., cov: 31)

Exomes 𝑓: 0.25 ( 46291 hom. )

Consequence

KLK4
NM_004917.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.895

Variant links:

Genes affected

KLK4 (HGNC:6365): (kallikrein related peptidase 4) 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 some tissues its expression is hormonally regulated. The expression pattern of a similar mouse protein in murine developing teeth supports a role for the protein in the degradation of enamel proteins. Several transcript variants encoding different proteins have been found for this gene. [provided by RefSeq, Dec 2014]

KLK4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 19-50910650-A-T is Benign according to our data. Variant chr19-50910650-A-T is described in ClinVar as [Benign]. Clinvar id is 1286882.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
KLK4	NM_004917.5 linkuse as main transcript	c.61+28T>A	intron_variant	ENST00000324041.6	NP_004908.4
KLK4	NM_001302961.2 linkuse as main transcript	c.-237+28T>A	intron_variant		NP_001289890.1
KLK4	XM_011527545.4 linkuse as main transcript	c.61+28T>A	intron_variant		XP_011525847.1
KLK4	NR_126566.2 linkuse as main transcript	n.61+28T>A	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
KLK4	ENST00000324041.6 linkuse as main transcript	c.61+28T>A	intron_variant	1	NM_004917.5	ENSP00000326159	P1
KLK4	ENST00000598305.5 linkuse as main transcript	c.-218+28T>A	intron_variant, NMD_transcript_variant	1		ENSP00000469963
KLK4	ENST00000602148.1 linkuse as main transcript	c.61+28T>A	intron_variant, NMD_transcript_variant	1		ENSP00000472091

Frequencies

GnomAD3 genomes

AF:

0.326

AC:

49488

AN:

151832

Hom.:

9462

Cov.:

show subpopulations

Gnomad AFR

AF:

0.540

Gnomad AMI

AF:

0.295

Gnomad AMR

AF:

0.262

Gnomad ASJ

AF:

0.222

Gnomad EAS

AF:

0.232

Gnomad SAS

AF:

0.323

Gnomad FIN

AF:

0.206

Gnomad MID

AF:

0.370

Gnomad NFE

AF:

0.242

Gnomad OTH

AF:

0.325

GnomAD3 exomes

AF:

0.266

AC:

42385

AN:

159112

Hom.:

6147

AF XY:

0.266

AC XY:

22248

AN XY:

83572

show subpopulations

Gnomad AFR exome

AF:

0.543

Gnomad AMR exome

AF:

0.217

Gnomad ASJ exome

AF:

0.219

Gnomad EAS exome

AF:

0.240

Gnomad SAS exome

AF:

0.334

Gnomad FIN exome

AF:

0.215

Gnomad NFE exome

AF:

0.245

Gnomad OTH exome

AF:

0.262

GnomAD4 exome

AF:

0.251

AC:

349958

AN:

1395372

Hom.:

46291

Cov.:

AF XY:

0.253

AC XY:

173964

AN XY:

688692

show subpopulations

Gnomad4 AFR exome

AF:

0.549

Gnomad4 AMR exome

AF:

0.228

Gnomad4 ASJ exome

AF:

0.217

Gnomad4 EAS exome

AF:

0.216

Gnomad4 SAS exome

AF:

0.330

Gnomad4 FIN exome

AF:

0.219

Gnomad4 NFE exome

AF:

0.239

Gnomad4 OTH exome

AF:

0.270

GnomAD4 genome

AF:

0.326

AC:

49561

AN:

151950

Hom.:

9489

Cov.:

AF XY:

0.322

AC XY:

23929

AN XY:

74258

show subpopulations

Gnomad4 AFR

AF:

0.540

Gnomad4 AMR

AF:

0.262

Gnomad4 ASJ

AF:

0.222

Gnomad4 EAS

AF:

0.233

Gnomad4 SAS

AF:

0.323

Gnomad4 FIN

AF:

0.206

Gnomad4 NFE

AF:

0.242

Gnomad4 OTH

AF:

0.326

Alfa

AF:

0.201

Hom.:

652

Bravo

AF:

0.337

Asia WGS

AF:

0.291

AC:

1013

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

5.8

DANN

Benign

0.83

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over