10-113709362-GAGA-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001227.5(CASP7):c.111-11664_111-11662del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00191 in 1,497,066 control chromosomes in the GnomAD database, including 51 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0019 (9 hom., cov: 33)
  • Exomes 𝑓: 0.0019 (42 hom.)
• Consequence: CASP7 NM_001227.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.43

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 10-113709362-GAGA-G is Benign according to our data. Variant chr10-113709362-GAGA-G is described in ClinVar as [Likely_benign]. Clinvar id is 2640853.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 281 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASP7	NM_001227.5	c.111-11664_111-11662del		intron_variant		ENST00000369318.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASP7	ENST00000369318.8	c.111-11664_111-11662del		intron_variant		1	NM_001227.5	P1

Frequencies

GnomAD3 genomes AF: 0.00185 AC: 281 AN: 152210 Hom.: 9 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.0542

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00538

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000808

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00489 AC: 501 AN: 102398 Hom.: 10 AF XY: 0.00487 AC XY: 274 AN XY: 56278

Gnomad AFR exome AF: 0.000193

Gnomad AMR exome AF: 0.00114

Gnomad ASJ exome AF: 0.0497

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00583

Gnomad FIN exome AF: 0.000234

Gnomad NFE exome AF: 0.00136

Gnomad OTH exome AF: 0.00479

GnomAD4 exome AF: 0.00191 AC: 2570 AN: 1344738 Hom.: 42 AF XY: 0.00212 AC XY: 1406 AN XY: 662192

Gnomad4 AFR exome AF: 0.000167

Gnomad4 AMR exome AF: 0.000724

Gnomad4 ASJ exome AF: 0.0479

Gnomad4 EAS exome AF: 0.0000574

Gnomad4 SAS exome AF: 0.00620

Gnomad4 FIN exome AF: 0.0000311

Gnomad4 NFE exome AF: 0.000619

Gnomad4 OTH exome AF: 0.00536

GnomAD4 genome AF: 0.00185 AC: 282 AN: 152328 Hom.: 9 Cov.: 33 AF XY: 0.00184 AC XY: 137 AN XY: 74480

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.0542

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00559

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000808

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00723 Hom.: 10

Bravo AF: 0.00176

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2023

CASP7: PM4:Supporting, BS1 -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs767845230; hg19: chr10-115469121;