chr19-15052105-T-A

Variant names:

• chr19-15052105-T-A
• rs2239364
• NM_012114.3:c.-46-101T>A

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.-46-101T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 732,860 control chromosomes in the GnomAD database, including 7,662 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1176 hom., cov: 31)
  • Exomes 𝑓: 0.14 (6486 hom.)
• Consequence: CASP14 NM_012114.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0980
• Publications: 2 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=-0.88).
• BP6: Variant 19-15052105-T-A is Benign according to our data. Variant chr19-15052105-T-A is described in ClinVar as Benign. ClinVar VariationId is 1238465.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.209 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.-46-101T>A		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.-46-101T>A		intron	N/A	ENSP00000393417.2	P31944
	ENSG00000302149	ENST00000784685.1		n.340+483A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17494 AN: 151952 Hom.: 1172 Cov.: 31

Gnomad AFR AF: 0.0611

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.0860

Gnomad ASJ AF: 0.0456

Gnomad EAS AF: 0.0770

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.101

GnomAD4 exome AF: 0.142 AC: 82200 AN: 580790 Hom.: 6486 AF XY: 0.144 AC XY: 44579 AN XY: 308734

African (AFR) AF: 0.0549 AC: 700 AN: 12746

American (AMR) AF: 0.0849 AC: 1392 AN: 16402

Ashkenazi Jewish (ASJ) AF: 0.0463 AC: 818 AN: 17678

East Asian (EAS) AF: 0.0978 AC: 2717 AN: 27770

South Asian (SAS) AF: 0.207 AC: 10438 AN: 50408

European-Finnish (FIN) AF: 0.171 AC: 7638 AN: 44624

Middle Eastern (MID) AF: 0.0730 AC: 232 AN: 3180

European-Non Finnish (NFE) AF: 0.144 AC: 54508 AN: 378064

Other (OTH) AF: 0.126 AC: 3757 AN: 29918

GnomAD4 genome AF: 0.115 AC: 17515 AN: 152070 Hom.: 1176 Cov.: 31 AF XY: 0.118 AC XY: 8737 AN XY: 74340

African (AFR) AF: 0.0616 AC: 2557 AN: 41494

American (AMR) AF: 0.0858 AC: 1311 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0456 AC: 158 AN: 3466

East Asian (EAS) AF: 0.0764 AC: 395 AN: 5172

South Asian (SAS) AF: 0.220 AC: 1061 AN: 4812

European-Finnish (FIN) AF: 0.170 AC: 1792 AN: 10546

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.144 AC: 9803 AN: 67986

Other (OTH) AF: 0.100 AC: 211 AN: 2110

Alfa AF: 0.136 Hom.: 178

Bravo AF: 0.105

Asia WGS AF: 0.149 AC: 523 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	-0.88
CADD	Benign	4.8
DANN	Benign	0.49
PhyloP100		0.098
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2239364; hg19: chr19-15162916; COSMIC: COSV107287532; COSMIC: COSV107287532;