rs3814231

Positions:

• chr10-113721259-C-T

Variant summary

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

The NM_001227.5(CASP7):​c.247+91C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 1,328,686 control chromosomes in the GnomAD database, including 46,378 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 (4451 hom., cov: 32)
  • Exomes 𝑓: 0.26 (41927 hom.)
• Consequence: CASP7 NM_001227.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.748

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASP7	NM_001227.5	c.247+91C>T		intron_variant		ENST00000369318.8	NP_001218.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASP7	ENST00000369318.8	c.247+91C>T		intron_variant		1	NM_001227.5	ENSP00000358324	P1

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35301 AN: 151966 Hom.: 4448 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.415

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.261

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.242

GnomAD4 exome AF: 0.261 AC: 307158 AN: 1176604 Hom.: 41927 AF XY: 0.261 AC XY: 152747 AN XY: 586338

Gnomad4 AFR exome AF: 0.134

Gnomad4 AMR exome AF: 0.283

Gnomad4 ASJ exome AF: 0.191

Gnomad4 EAS exome AF: 0.436

Gnomad4 SAS exome AF: 0.263

Gnomad4 FIN exome AF: 0.271

Gnomad4 NFE exome AF: 0.258

Gnomad4 OTH exome AF: 0.253

GnomAD4 genome AF: 0.232 AC: 35314 AN: 152082 Hom.: 4451 Cov.: 32 AF XY: 0.234 AC XY: 17407 AN XY: 74318

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.254

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.415

Gnomad4 SAS AF: 0.271

Gnomad4 FIN AF: 0.270

Gnomad4 NFE AF: 0.261

Gnomad4 OTH AF: 0.244

Alfa AF: 0.256 Hom.: 5926

Bravo AF: 0.228

Asia WGS AF: 0.302 AC: 1049 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.96
DANN	Benign	0.57

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: rs3814231; hg19: chr10-115481018; COSMIC: COSV61881348; COSMIC: COSV61881348;