10-113729830-T-C

Variant names:

• chr10-113729830-T-C
• rs4353229
• NM_001227.5:c.*290T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000369318.8(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 ENST00000369318.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.323
• Publications: 38 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000369318.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASP7	NM_001227.5	MANE Select	c.*290T>C		3_prime_UTR	Exon 7 of 7	NP_001218.1
	CASP7	NM_001267057.1		c.*290T>C		3_prime_UTR	Exon 7 of 7	NP_001253986.1
	CASP7	NM_033338.6		c.*290T>C		3_prime_UTR	Exon 8 of 8	NP_203124.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASP7	ENST00000369318.8	TSL:1 MANE Select	c.*290T>C		3_prime_UTR	Exon 7 of 7	ENSP00000358324.4
	CASP7	ENST00000621607.4	TSL:1	c.*290T>C		3_prime_UTR	Exon 7 of 7	ENSP00000478999.1
	CASP7	ENST00000345633.8	TSL:1	c.*290T>C		3_prime_UTR	Exon 8 of 8	ENSP00000298701.7

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

African (AFR) AF: 0.140 AC: 1051 AN: 7498

American (AMR) AF: 0.251 AC: 2374 AN: 9442

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 1288 AN: 7182

East Asian (EAS) AF: 0.434 AC: 5703 AN: 13146

South Asian (SAS) AF: 0.207 AC: 5881 AN: 28408

European-Finnish (FIN) AF: 0.261 AC: 2857 AN: 10942

Middle Eastern (MID) AF: 0.182 AC: 182 AN: 998

European-Non Finnish (NFE) AF: 0.248 AC: 34236 AN: 138126

Other (OTH) AF: 0.236 AC: 3101 AN: 13134

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

African (AFR) AF: 0.146 AC: 6075 AN: 41530

American (AMR) AF: 0.239 AC: 3647 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 639 AN: 3470

East Asian (EAS) AF: 0.421 AC: 2173 AN: 5166

South Asian (SAS) AF: 0.237 AC: 1145 AN: 4824

European-Finnish (FIN) AF: 0.272 AC: 2877 AN: 10582

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.262 AC: 17825 AN: 67988

Other (OTH) AF: 0.225 AC: 476 AN: 2114

Alfa AF: 0.253 Hom.: 17653

Bravo AF: 0.227

Asia WGS AF: 0.280 AC: 975 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	15
DANN	Benign	0.89
PhyloP100		0.32
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4353229; hg19: chr10-115489589;