19-15053211-T-G

Variant names:

• chr19-15053211-T-G
• rs3181307
• NM_012114.3:c.28-271T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 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 -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 VariationId 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.

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.28-271T>G		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.28-271T>G		intron	N/A	ENSP00000393417.2	P31944
	ENSG00000302149	ENST00000784685.1		n.233-516A>C		intron	N/A

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

African (AFR) AF: 0.581 AC: 24013 AN: 41358

American (AMR) AF: 0.396 AC: 6037 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 1709 AN: 3466

East Asian (EAS) AF: 0.407 AC: 2088 AN: 5124

South Asian (SAS) AF: 0.407 AC: 1950 AN: 4792

European-Finnish (FIN) AF: 0.488 AC: 5152 AN: 10550

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.449 AC: 30513 AN: 67910

Other (OTH) AF: 0.488 AC: 1024 AN: 2100

Alfa AF: 0.324 Hom.: 825

Bravo AF: 0.480

Asia WGS AF: 0.437 AC: 1521 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.33
DANN	Benign	0.049
PhyloP100		-3.9
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: rs3181307; hg19: chr19-15164022; COSMIC: COSV55666366; COSMIC: COSV55666366;