19-15051947-A-G

Position:

• chr19-15051947-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_012114.3(CASP14):​c.-46-259A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 151,436 control chromosomes in the GnomAD database, including 17,278 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.47 (17278 hom., cov: 29)
• Consequence: CASP14 NM_012114.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.303

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BP6: Variant 19-15051947-A-G is Benign according to our data. Variant chr19-15051947-A-G is described in ClinVar as [Benign]. Clinvar id is 1247864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASP14	NM_012114.3	c.-46-259A>G		intron_variant		ENST00000427043.4	NP_036246.1
CASP14	XM_011527861.2	c.-46-259A>G		intron_variant			XP_011526163.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASP14	ENST00000427043.4	c.-46-259A>G		intron_variant		1	NM_012114.3	ENSP00000393417	P1

Frequencies

GnomAD3 genomes AF: 0.475 AC: 71845 AN: 151318 Hom.: 17267 Cov.: 29

Gnomad AFR AF: 0.561

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.492

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.485

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.483

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

GnomAD4 genome AF: 0.475 AC: 71890 AN: 151436 Hom.: 17278 Cov.: 29 AF XY: 0.472 AC XY: 34886 AN XY: 73950

Gnomad4 AFR AF: 0.561

Gnomad4 AMR AF: 0.395

Gnomad4 ASJ AF: 0.492

Gnomad4 EAS AF: 0.402

Gnomad4 SAS AF: 0.406

Gnomad4 FIN AF: 0.485

Gnomad4 NFE AF: 0.448

Gnomad4 OTH AF: 0.480

Alfa AF: 0.452 Hom.: 14626

Bravo AF: 0.474

Asia WGS AF: 0.436 AC: 1516 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-1.0
CADD	Benign	1.9
DANN	Benign	0.25

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: rs2158468; hg19: chr19-15162758;