10-113729830-T-C

Position:

• chr10-113729830-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001227.5(CASP7):​c.*290T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 381,040 control chromosomes in the GnomAD database, including 11,751 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 0.23 (4434 hom., cov: 32)
  • Exomes 𝑓: 0.25 (7317 hom.)
• Consequence: CASP7 NM_001227.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.323

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASP7	NM_001227.5	c.*290T>C		3_prime_UTR_variant	7/7	ENST00000369318.8	NP_001218.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASP7	ENST00000369318.8	c.*290T>C		3_prime_UTR_variant	7/7	1	NM_001227.5	ENSP00000358324.4

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35274 AN: 152046 Hom.: 4430 Cov.: 32

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.225

GnomAD4 exome AF: 0.248 AC: 56673 AN: 228876 Hom.: 7317 Cov.: 0 AF XY: 0.244 AC XY: 29447 AN XY: 120610

Gnomad4 AFR exome AF: 0.140

Gnomad4 AMR exome AF: 0.251

Gnomad4 ASJ exome AF: 0.179

Gnomad4 EAS exome AF: 0.434

Gnomad4 SAS exome AF: 0.207

Gnomad4 FIN exome AF: 0.261

Gnomad4 NFE exome AF: 0.248

Gnomad4 OTH exome AF: 0.236

GnomAD4 genome AF: 0.232 AC: 35290 AN: 152164 Hom.: 4434 Cov.: 32 AF XY: 0.233 AC XY: 17338 AN XY: 74390

Gnomad4 AFR AF: 0.146

Gnomad4 AMR AF: 0.239

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.421

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.272

Gnomad4 NFE AF: 0.262

Gnomad4 OTH AF: 0.225

Alfa AF: 0.252 Hom.: 7693

Bravo AF: 0.227

Asia WGS AF: 0.280 AC: 975 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	15
DANN	Benign	0.89

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: rs4353229; hg19: chr10-115489589;