10-113729495-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001227.5(CASP7):c.867C>T(p.Pro289=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00162 in 1,614,182 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0016 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (8 hom.)
• Consequence: CASP7 NM_001227.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.58

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 10-113729495-C-T is Benign according to our data. Variant chr10-113729495-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2640855.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.58 with no splicing effect.
• BS2: High AC in GnomAd at 250 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASP7	NM_001227.5	c.867C>T	p.Pro289=	synonymous_variant	7/7	ENST00000369318.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASP7	ENST00000369318.8	c.867C>T	p.Pro289=	synonymous_variant	7/7	1	NM_001227.5	P1

Frequencies

GnomAD3 genomes AF: 0.00164 AC: 250 AN: 152190 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00569

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00435

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00163

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.00209 AC: 525 AN: 251428 Hom.: 4 AF XY: 0.00247 AC XY: 335 AN XY: 135884

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.00150

Gnomad ASJ exome AF: 0.000595

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00679

Gnomad FIN exome AF: 0.000231

Gnomad NFE exome AF: 0.00204

Gnomad OTH exome AF: 0.00293

GnomAD4 exome AF: 0.00162 AC: 2365 AN: 1461874 Hom.: 8 Cov.: 32 AF XY: 0.00188 AC XY: 1369 AN XY: 727240

Gnomad4 AFR exome AF: 0.000239

Gnomad4 AMR exome AF: 0.00154

Gnomad4 ASJ exome AF: 0.000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00660

Gnomad4 FIN exome AF: 0.000150

Gnomad4 NFE exome AF: 0.00137

Gnomad4 OTH exome AF: 0.00200

GnomAD4 genome AF: 0.00164 AC: 250 AN: 152308 Hom.: 1 Cov.: 33 AF XY: 0.00196 AC XY: 146 AN XY: 74488

Gnomad4 AFR AF: 0.000337

Gnomad4 AMR AF: 0.00569

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00435

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00163

Gnomad4 OTH AF: 0.00425

Alfa AF: 0.00150 Hom.: 1

Bravo AF: 0.00150

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00316

EpiControl AF: 0.00338

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, 2022

CASP7: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	0.0050
Dann	Benign	0.47

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: rs61755279; hg19: chr10-115489254; COSMIC: COSV100615103; COSMIC: COSV100615103;