19-15051944-C-T

Variant names:

• chr19-15051944-C-T
• rs2158467
• NM_012114.3:c.-46-262C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_012114.3(CASP14):​c.-46-262C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 151,378 control chromosomes in the GnomAD database, including 6,913 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.29 (6913 hom., cov: 29)
• Consequence: CASP14 NM_012114.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.30
• Publications: 1 publications found

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]

ENSG00000302149 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 19-15051944-C-T is Benign according to our data. Variant chr19-15051944-C-T is described in ClinVar as Benign. ClinVar VariationId is 1287531.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012114.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASP14	NM_012114.3	MANE Select	c.-46-262C>T		intron	N/A	NP_036246.1	P31944

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASP14	ENST00000427043.4	TSL:1 MANE Select	c.-46-262C>T		intron	N/A	ENSP00000393417.2	P31944
	ENSG00000302149	ENST00000784685.1		n.340+644G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43199 AN: 151254 Hom.: 6908 Cov.: 29

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.286

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

GnomAD4 genome AF: 0.285 AC: 43209 AN: 151378 Hom.: 6913 Cov.: 29 AF XY: 0.287 AC XY: 21190 AN XY: 73936

African (AFR) AF: 0.137 AC: 5638 AN: 41304

American (AMR) AF: 0.272 AC: 4136 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 1243 AN: 3460

East Asian (EAS) AF: 0.382 AC: 1945 AN: 5098

South Asian (SAS) AF: 0.270 AC: 1293 AN: 4784

European-Finnish (FIN) AF: 0.421 AC: 4396 AN: 10436

Middle Eastern (MID) AF: 0.313 AC: 90 AN: 288

European-Non Finnish (NFE) AF: 0.348 AC: 23591 AN: 67804

Other (OTH) AF: 0.288 AC: 603 AN: 2096

Alfa AF: 0.186 Hom.: 413

Bravo AF: 0.273

Asia WGS AF: 0.328 AC: 1137 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.9
DANN	Benign	0.54
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2158467; hg19: chr19-15162755;