rs12416109

Positions:

• chr10-113724901-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001227.5(CASP7):​c.377-461G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 151,946 control chromosomes in the GnomAD database, including 17,659 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 0.48 (17659 hom., cov: 32)
• Consequence: CASP7 NM_001227.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28

Genes affected

CASP7 (HGNC:1508): (caspase 7) 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. The precursor of the encoded protein is cleaved by caspase 3 and 10, is activated upon cell death stimuli and induces apoptosis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, May 2012]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASP7	NM_001227.5	c.377-461G>A		intron_variant		ENST00000369318.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASP7	ENST00000369318.8	c.377-461G>A		intron_variant		1	NM_001227.5	P1

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72791 AN: 151828 Hom.: 17636 Cov.: 32

Gnomad AFR AF: 0.486

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.429

Gnomad EAS AF: 0.637

Gnomad SAS AF: 0.447

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.486

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

GnomAD4 genome AF: 0.480 AC: 72859 AN: 151946 Hom.: 17659 Cov.: 32 AF XY: 0.476 AC XY: 35315 AN XY: 74262

Gnomad4 AFR AF: 0.487

Gnomad4 AMR AF: 0.421

Gnomad4 ASJ AF: 0.429

Gnomad4 EAS AF: 0.636

Gnomad4 SAS AF: 0.447

Gnomad4 FIN AF: 0.427

Gnomad4 NFE AF: 0.488

Gnomad4 OTH AF: 0.483

Alfa AF: 0.484 Hom.: 16684

Bravo AF: 0.480

Asia WGS AF: 0.512 AC: 1777 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	19
DANN	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.39		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.26		Position offset: -44
DS_DG_spliceai		0.39		Position offset: 1

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

Publications

LitVar

Other links and lift over

dbSNP: rs12416109; hg19: chr10-115484660;