19-15053309-T-C

Position:

• chr19-15053309-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_012114.3(CASP14):​c.28-173T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0648 in 152,150 control chromosomes in the GnomAD database, including 833 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.065 (833 hom., cov: 32)
• Consequence: CASP14 NM_012114.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.122

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 19-15053309-T-C is Benign according to our data. Variant chr19-15053309-T-C is described in ClinVar as [Benign]. Clinvar id is 1251768.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASP14	NM_012114.3	c.28-173T>C		intron_variant		ENST00000427043.4	NP_036246.1
CASP14	XM_011527861.2	c.28-173T>C		intron_variant			XP_011526163.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASP14	ENST00000427043.4	c.28-173T>C		intron_variant		1	NM_012114.3	ENSP00000393417.2

Frequencies

GnomAD3 genomes AF: 0.0647 AC: 9843 AN: 152032 Hom.: 832 Cov.: 32

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0281

Gnomad ASJ AF: 0.0225

Gnomad EAS AF: 0.0197

Gnomad SAS AF: 0.0818

Gnomad FIN AF: 0.00198

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.00666

Gnomad OTH AF: 0.0665

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0648 AC: 9859 AN: 152150 Hom.: 833 Cov.: 32 AF XY: 0.0642 AC XY: 4780 AN XY: 74398

Gnomad4 AFR AF: 0.198

Gnomad4 AMR AF: 0.0280

Gnomad4 ASJ AF: 0.0225

Gnomad4 EAS AF: 0.0195

Gnomad4 SAS AF: 0.0821

Gnomad4 FIN AF: 0.00198

Gnomad4 NFE AF: 0.00666

Gnomad4 OTH AF: 0.0649

Alfa AF: 0.0403 Hom.: 63

Bravo AF: 0.0704

Asia WGS AF: 0.0630 AC: 220 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.4
DANN	Benign	0.78

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

Other links and lift over

dbSNP: rs3181308; hg19: chr19-15164120;