10-113729891-T-G

Position:

• chr10-113729891-T-G

Variant summary

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

The NM_001227.5(CASP7):​c.*351T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 231,012 control chromosomes in the GnomAD database, including 17,205 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 0.37 (10972 hom., cov: 32)
  • Exomes 𝑓: 0.39 (6233 hom.)
• Consequence: CASP7 NM_001227.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASP7	NM_001227.5	c.*351T>G		3_prime_UTR_variant	7/7	ENST00000369318.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASP7	ENST00000369318.8	c.*351T>G		3_prime_UTR_variant	7/7	1	NM_001227.5	P1

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56776 AN: 151932 Hom.: 10974 Cov.: 32

Gnomad AFR AF: 0.429

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.378

GnomAD4 exome AF: 0.390 AC: 30805 AN: 78962 Hom.: 6233 Cov.: 0 AF XY: 0.389 AC XY: 15945 AN XY: 40938

Gnomad4 AFR exome AF: 0.461

Gnomad4 AMR exome AF: 0.483

Gnomad4 ASJ exome AF: 0.468

Gnomad4 EAS exome AF: 0.215

Gnomad4 SAS exome AF: 0.436

Gnomad4 FIN exome AF: 0.432

Gnomad4 NFE exome AF: 0.379

Gnomad4 OTH exome AF: 0.407

GnomAD4 genome AF: 0.374 AC: 56803 AN: 152050 Hom.: 10972 Cov.: 32 AF XY: 0.377 AC XY: 27990 AN XY: 74316

Gnomad4 AFR AF: 0.429

Gnomad4 AMR AF: 0.462

Gnomad4 ASJ AF: 0.428

Gnomad4 EAS AF: 0.185

Gnomad4 SAS AF: 0.377

Gnomad4 FIN AF: 0.382

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.380

Alfa AF: 0.350 Hom.: 11051

Bravo AF: 0.382

Asia WGS AF: 0.320 AC: 1112 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.9
DANN	Benign	0.50

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: rs10787498; hg19: chr10-115489650;