rs1127687

Positions:

• chr10-113730350-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.*810G>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 0.231 in 152,444 control chromosomes in the GnomAD database, including 4,288 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 (4281 hom., cov: 32)
  • Exomes 𝑓: 0.18 (7 hom.)
• Consequence: CASP7 NM_001227.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0390

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASP7	NM_001227.5	c.*810G>A		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.*810G>A		3_prime_UTR_variant	7/7	1	NM_001227.5	ENSP00000358324	P1

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35070 AN: 151994 Hom.: 4265 Cov.: 32

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.247

GnomAD4 exome AF: 0.184 AC: 61 AN: 332 Hom.: 7 Cov.: 0 AF XY: 0.185 AC XY: 43 AN XY: 232

Gnomad4 AFR exome AF: 0.750

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.156

Gnomad4 NFE exome AF: 0.189

Gnomad4 OTH exome AF: 0.300

GnomAD4 genome AF: 0.231 AC: 35122 AN: 152112 Hom.: 4281 Cov.: 32 AF XY: 0.226 AC XY: 16817 AN XY: 74366

Gnomad4 AFR AF: 0.295

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.221

Gnomad4 SAS AF: 0.221

Gnomad4 FIN AF: 0.135

Gnomad4 NFE AF: 0.220

Gnomad4 OTH AF: 0.244

Alfa AF: 0.225 Hom.: 4068

Bravo AF: 0.235

Asia WGS AF: 0.236 AC: 819 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.3
DANN	Benign	0.39

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: rs1127687; hg19: chr10-115490109;