rs5030551

Positions:

• chr4-109697894-G-A

Variant summary

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

The NM_001226.4(CASP6):​c.84-126C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00587 in 1,047,886 control chromosomes in the GnomAD database, including 249 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 0.025 (172 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (77 hom.)
• Consequence: CASP6 NM_001226.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.850

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=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0856 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASP6	NM_001226.4	c.84-126C>T		intron_variant		ENST00000265164.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASP6	ENST00000265164.7	c.84-126C>T		intron_variant		1	NM_001226.4	P1
CASP6	ENST00000352981.7	c.41-3194C>T		intron_variant		1
CASP6	ENST00000503684.5	c.30-126C>T		intron_variant		3
CASP6	ENST00000505486.1	c.84-126C>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.0250 AC: 3807 AN: 152146 Hom.: 172 Cov.: 32

Gnomad AFR AF: 0.0880

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00694

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.0158

GnomAD4 exome AF: 0.00261 AC: 2338 AN: 895622 Hom.: 77 AF XY: 0.00235 AC XY: 1064 AN XY: 452902

Gnomad4 AFR exome AF: 0.0873

Gnomad4 AMR exome AF: 0.00415

Gnomad4 ASJ exome AF: 0.000176

Gnomad4 EAS exome AF: 0.0000292

Gnomad4 SAS exome AF: 0.000254

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000299

Gnomad4 OTH exome AF: 0.00552

GnomAD4 genome AF: 0.0251 AC: 3817 AN: 152264 Hom.: 172 Cov.: 32 AF XY: 0.0233 AC XY: 1736 AN XY: 74456

Gnomad4 AFR AF: 0.0880

Gnomad4 AMR AF: 0.00693

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000294

Gnomad4 OTH AF: 0.0156

Alfa AF: 0.0131 Hom.: 14

Bravo AF: 0.0285

Asia WGS AF: 0.00520 AC: 19 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.98
DANN	Benign	0.79

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: rs5030551; hg19: chr4-110619050;