XM_047416244.1:c.16+1292G>A

Variant names:

• chr4-109707163-C-T
• rs7694620
• XM_047416244.1:c.16+1292G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_047416244.1(CASP6):​c.16+1292G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.678 in 152,128 control chromosomes in the GnomAD database, including 35,806 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 0.68 (35806 hom., cov: 32)
• Consequence: CASP6 XM_047416244.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Variant Effect in Transcripts

 

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Frequencies

GnomAD3 genomes AF: 0.678 AC: 103049 AN: 152010 Hom.: 35730 Cov.: 32

Gnomad AFR AF: 0.833

Gnomad AMI AF: 0.684

Gnomad AMR AF: 0.580

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.565

Gnomad SAS AF: 0.737

Gnomad FIN AF: 0.662

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.619

Gnomad OTH AF: 0.640

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

GnomAD4 genome AF: 0.678 AC: 103184 AN: 152128 Hom.: 35806 Cov.: 32 AF XY: 0.678 AC XY: 50399 AN XY: 74352

African (AFR) AF: 0.833 AC: 34576 AN: 41498

American (AMR) AF: 0.580 AC: 8873 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.579 AC: 2003 AN: 3462

East Asian (EAS) AF: 0.566 AC: 2926 AN: 5168

South Asian (SAS) AF: 0.738 AC: 3562 AN: 4828

European-Finnish (FIN) AF: 0.662 AC: 6996 AN: 10570

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.619 AC: 42086 AN: 68000

Other (OTH) AF: 0.645 AC: 1362 AN: 2112

Alfa AF: 0.640 Hom.: 18176

Bravo AF: 0.674

Asia WGS AF: 0.709 AC: 2463 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	8.8
DANN	Benign	0.88
PhyloP100		-1.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7694620; hg19: chr4-110628319;