rs1042891

Positions:

• chr4-109688930-A-G
• chr4-109688930-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001226.4(CASP6):​c.*400T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.687 in 156,256 control chromosomes in the GnomAD database, including 37,276 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.69 (36217 hom., cov: 28)
  • Exomes 𝑓: 0.62 (1059 hom.)
• Consequence: CASP6 NM_001226.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73

Genes affected

CASP6 (HGNC:1507): (caspase 6) This gene encodes a member of the cysteine-aspartic acid protease (caspase) family of enzymes. 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 acid residues to produce two subunits, large and small, that dimerize to form the active enzyme. This protein is processed by caspases 7, 8 and 10, and is thought to function as a downstream enzyme in the caspase activation cascade. Alternative splicing of this gene results in multiple transcript variants that encode different isoforms. [provided by RefSeq, Oct 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.776 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASP6	NM_001226.4	c.*400T>C		3_prime_UTR_variant	7/7	ENST00000265164.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASP6	ENST00000265164.7	c.*400T>C		3_prime_UTR_variant	7/7	1	NM_001226.4	P1
CASP6	ENST00000352981.7	c.*400T>C		3_prime_UTR_variant	4/4	1
CASP6	ENST00000507550.5	n.864T>C		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.689 AC: 103901 AN: 150788 Hom.: 36169 Cov.: 28

Gnomad AFR AF: 0.783

Gnomad AMI AF: 0.687

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.533

Gnomad SAS AF: 0.738

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.664

Gnomad OTH AF: 0.669

GnomAD4 exome AF: 0.615 AC: 3298 AN: 5362 Hom.: 1059 Cov.: 0 AF XY: 0.611 AC XY: 1699 AN XY: 2780

Gnomad4 AFR exome AF: 0.662

Gnomad4 AMR exome AF: 0.586

Gnomad4 ASJ exome AF: 0.432

Gnomad4 EAS exome AF: 0.463

Gnomad4 SAS exome AF: 0.668

Gnomad4 FIN exome AF: 0.565

Gnomad4 NFE exome AF: 0.642

Gnomad4 OTH exome AF: 0.616

GnomAD4 genome AF: 0.689 AC: 104000 AN: 150894 Hom.: 36217 Cov.: 28 AF XY: 0.686 AC XY: 50519 AN XY: 73602

Gnomad4 AFR AF: 0.783

Gnomad4 AMR AF: 0.620

Gnomad4 ASJ AF: 0.597

Gnomad4 EAS AF: 0.534

Gnomad4 SAS AF: 0.739

Gnomad4 FIN AF: 0.673

Gnomad4 NFE AF: 0.664

Gnomad4 OTH AF: 0.673

Alfa AF: 0.685 Hom.: 7686

Bravo AF: 0.687

Asia WGS AF: 0.702 AC: 2439 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.36
DANN	Benign	0.45

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: rs1042891; hg19: chr4-110610086; COSMIC: COSV54461286; COSMIC: COSV54461286;