chr19-15053211-T-G

Position:

• chr19-15053211-T-G

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.28-271T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 151,746 control chromosomes in the GnomAD database, including 17,909 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.48 (17909 hom., cov: 30)
• Consequence: CASP14 NM_012114.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.92

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=-1.06).
• BP6: Variant 19-15053211-T-G is Benign according to our data. Variant chr19-15053211-T-G is described in ClinVar as [Benign]. Clinvar id is 1228577.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASP14	NM_012114.3	c.28-271T>G		intron_variant		ENST00000427043.4	NP_036246.1
CASP14	XM_011527861.2	c.28-271T>G		intron_variant			XP_011526163.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASP14	ENST00000427043.4	c.28-271T>G		intron_variant		1	NM_012114.3	ENSP00000393417.2

Frequencies

GnomAD3 genomes AF: 0.481 AC: 72983 AN: 151628 Hom.: 17897 Cov.: 30

Gnomad AFR AF: 0.581

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.408

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.449

Gnomad OTH AF: 0.490

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

GnomAD4 genome AF: 0.481 AC: 73031 AN: 151746 Hom.: 17909 Cov.: 30 AF XY: 0.478 AC XY: 35466 AN XY: 74154

Gnomad4 AFR AF: 0.581

Gnomad4 AMR AF: 0.396

Gnomad4 ASJ AF: 0.493

Gnomad4 EAS AF: 0.407

Gnomad4 SAS AF: 0.407

Gnomad4 FIN AF: 0.488

Gnomad4 NFE AF: 0.449

Gnomad4 OTH AF: 0.488

Alfa AF: 0.306 Hom.: 695

Bravo AF: 0.480

Asia WGS AF: 0.437 AC: 1521 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

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.33
DANN	Benign	0.049

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

Other links and lift over

dbSNP: rs3181307; hg19: chr19-15164022; COSMIC: COSV55666366; COSMIC: COSV55666366;