rs768063

Variant names:

• chr4-109699300-T-C
• rs768063
• NM_001226.4:c.41-958A>G

Variant summary

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

The NM_001226.4(CASP6):​c.41-958A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.976 in 152,278 control chromosomes in the GnomAD database, including 72,482 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 0.98 (72482 hom., cov: 31)
• Consequence: CASP6 NM_001226.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28

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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.986 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASP6	NM_001226.4	c.41-958A>G		intron_variant	Intron 1 of 6	ENST00000265164.7	NP_001217.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASP6	ENST00000265164.7	c.41-958A>G		intron_variant	Intron 1 of 6	1	NM_001226.4	ENSP00000265164.2
CASP6	ENST00000352981.7	c.40+4056A>G		intron_variant	Intron 1 of 3	1		ENSP00000285333.3
CASP6	ENST00000503684.5	c.-14-958A>G		intron_variant	Intron 1 of 4	3		ENSP00000427669.1
CASP6	ENST00000505486.1	c.41-958A>G		intron_variant	Intron 1 of 3	4		ENSP00000424080.1

Frequencies

GnomAD3 genomes AF: 0.976 AC: 148434 AN: 152160 Hom.: 72421 Cov.: 31

Gnomad AFR AF: 0.994

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.978

Gnomad ASJ AF: 0.918

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.944

Gnomad FIN AF: 0.986

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.965

Gnomad OTH AF: 0.976

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

GnomAD4 genome AF: 0.976 AC: 148554 AN: 152278 Hom.: 72482 Cov.: 31 AF XY: 0.976 AC XY: 72646 AN XY: 74460

Gnomad4 AFR AF: 0.994

Gnomad4 AMR AF: 0.978

Gnomad4 ASJ AF: 0.918

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.944

Gnomad4 FIN AF: 0.986

Gnomad4 NFE AF: 0.965

Gnomad4 OTH AF: 0.976

Alfa AF: 0.965 Hom.: 62819

Bravo AF: 0.977

Asia WGS AF: 0.981 AC: 3412 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.015
DANN	Benign	0.42

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: rs768063; hg19: chr4-110620456;