Variant 19-15053628-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_012114.3(CASP14):c.174C>T(p.Ala58Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00382 in 1,614,062 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0025 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0040 ( 18 hom. )

Consequence

CASP14
NM_012114.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.305

Variant links:

Genes affected

CASP14 (HGNC:1502): (caspase 14) This gene encodes a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes which undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. This caspase has been shown to be processed and activated by caspase 8 and caspase 10 in vitro, and by anti-Fas agonist antibody or TNF-related apoptosis inducing ligand in vivo. The expression and processing of this caspase may be involved in keratinocyte terminal differentiation, which is important for the formation of the skin barrier. [provided by RefSeq, Jul 2008]

CASP14 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 19-15053628-C-T is Benign according to our data. Variant chr19-15053628-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 770655.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.305 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASP14	NM_012114.3 linkuse as main transcript	c.174C>T	p.Ala58Ala	synonymous_variant	3/7	ENST00000427043.4	NP_036246.1
CASP14	XM_011527861.2 linkuse as main transcript	c.174C>T	p.Ala58Ala	synonymous_variant	3/6		XP_011526163.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASP14	ENST00000427043.4 linkuse as main transcript	c.174C>T	p.Ala58Ala	synonymous_variant	3/7	1	NM_012114.3	ENSP00000393417.2		P31944

Frequencies

GnomAD3 genomes

AF:

0.00254

AC:

387

AN:

152066

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000580

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.000566

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00468

Gnomad OTH

AF:

0.00288

GnomAD3 exomes

AF:

0.00234

AC:

587

AN:

251250

Hom.:

AF XY:

0.00239

AC XY:

325

AN XY:

135808

show subpopulations

Gnomad AFR exome

AF:

0.000740

Gnomad AMR exome

AF:

0.00162

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00252

Gnomad FIN exome

AF:

0.000555

Gnomad NFE exome

AF:

0.00368

Gnomad OTH exome

AF:

0.00180

GnomAD4 exome

AF:

0.00395

AC:

5776

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00389

AC XY:

2832

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.000478

Gnomad4 AMR exome

AF:

0.00183

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00260

Gnomad4 FIN exome

AF:

0.000861

Gnomad4 NFE exome

AF:

0.00470

Gnomad4 OTH exome

AF:

0.00300

GnomAD4 genome

AF:

0.00254

AC:

387

AN:

152184

Hom.:

Cov.:

AF XY:

0.00212

AC XY:

158

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.000578

Gnomad4 AMR

AF:

0.00164

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.000566

Gnomad4 NFE

AF:

0.00468

Gnomad4 OTH

AF:

0.00285

Alfa

AF:

0.00375

Hom.:

Bravo

AF:

0.00247

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00371

EpiControl

AF:

0.00385

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 29, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2023	CASP14: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.75

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over