Variant 19-15053631-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_012114.3(CASP14):c.177G>A(p.Glu59=) variant causes a splice region, synonymous change. The variant allele was found at a frequency of 0.00152 in 1,614,150 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 1 hom. )

Consequence

CASP14
NM_012114.3 splice_region, synonymous

Scores

Splicing: ADA: 1.000

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.94

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP6

Variant 19-15053631-G-A is Benign according to our data. Variant chr19-15053631-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 713661.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASP14	NM_012114.3 linkuse as main transcript	c.177G>A	p.Glu59=	splice_region_variant, synonymous_variant	3/7	ENST00000427043.4	NP_036246.1
CASP14	XM_011527861.2 linkuse as main transcript	c.177G>A	p.Glu59=	splice_region_variant, 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.177G>A	p.Glu59=	splice_region_variant, synonymous_variant	3/7	1	NM_012114.3	ENSP00000393417	P1

Frequencies

GnomAD3 genomes

AF:

0.00123

AC:

187

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00237

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000955

AC:

240

AN:

251260

Hom.:

AF XY:

0.000876

AC XY:

119

AN XY:

135826

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000231

Gnomad ASJ exome

AF:

0.000794

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00190

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.00156

AC:

2274

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00150

AC XY:

1093

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.000842

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000936

Gnomad4 NFE exome

AF:

0.00195

Gnomad4 OTH exome

AF:

0.000911

GnomAD4 genome

AF:

0.00123

AC:

187

AN:

152268

Hom.:

Cov.:

AF XY:

0.00107

AC XY:

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.000481

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00237

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00168

Hom.:

Bravo

AF:

0.00102

EpiCase

AF:

0.00147

EpiControl

AF:

0.00148

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

DANN

Benign

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.98

SpliceAI score (max)

0.54

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.54

Position offset: 8

DS_DL_spliceai

0.20

Position offset: 0

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