rs11196422

chr10-113683331-G-A

Variant summary

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

The NM_001227.5(CASP7):c.-1+3353G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 151,866 control chromosomes in the GnomAD database, including 2,572 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 0.17 (2572 hom., cov: 32)
• Consequence: CASP7 NM_001227.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.422

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASP7	NM_001227.5	c.-1+3353G>A		intron_variant		ENST00000369318.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASP7	ENST00000369318.8	c.-1+3353G>A		intron_variant		1	NM_001227.5	P1

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25893 AN: 151748 Hom.: 2569 Cov.: 32

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.0967

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.171 AC: 25929 AN: 151866 Hom.: 2572 Cov.: 32 AF XY: 0.169 AC XY: 12551 AN XY: 74222

Gnomad4 AFR AF: 0.266

Gnomad4 AMR AF: 0.138

Gnomad4 ASJ AF: 0.228

Gnomad4 EAS AF: 0.156

Gnomad4 SAS AF: 0.164

Gnomad4 FIN AF: 0.135

Gnomad4 NFE AF: 0.124

Gnomad4 OTH AF: 0.186

Alfa AF: 0.136 Hom.: 3007

Bravo AF: 0.174

Asia WGS AF: 0.176 AC: 611 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	3.1
Dann	Benign	0.77

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: rs11196422; hg19: chr10-115443090;