rs12247479

chr10-113730301-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.*761G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,536 control chromosomes in the GnomAD database, including 2,294 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 0.16 (2292 hom., cov: 32)
  • Exomes 𝑓: 0.11 (2 hom.)
• Consequence: CASP7 NM_001227.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.402

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASP7	NM_001227.5	c.*761G>A		3_prime_UTR_variant	7/7	ENST00000369318.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASP7	ENST00000369318.8	c.*761G>A		3_prime_UTR_variant	7/7	1	NM_001227.5	P1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24596 AN: 152078 Hom.: 2291 Cov.: 32

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.0965

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.183

GnomAD4 exome AF: 0.115 AC: 39 AN: 340 Hom.: 2 Cov.: 0 AF XY: 0.127 AC XY: 31 AN XY: 244

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.143

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.333

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.101

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.162 AC: 24613 AN: 152196 Hom.: 2292 Cov.: 32 AF XY: 0.160 AC XY: 11899 AN XY: 74418

Gnomad4 AFR AF: 0.252

Gnomad4 AMR AF: 0.134

Gnomad4 ASJ AF: 0.219

Gnomad4 EAS AF: 0.115

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.185

Alfa AF: 0.136 Hom.: 1612

Bravo AF: 0.166

Asia WGS AF: 0.158 AC: 549 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	3.0
Dann	Benign	0.41

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: rs12247479; hg19: chr10-115490060;