ENST00000345633.8:c.-282G>T

Variant names:

• chr10-113679771-G-T
• rs28411397
• ENST00000345633.8:c.-282G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000345633.8(CASP7):​c.-282G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000866 in 1,154,560 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 8.7e-7 (0 hom.)
• Consequence: CASP7 ENST00000345633.8 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.21
• Publications: 15 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13997638).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASP7	NM_001227.5	c.-208G>T		upstream_gene_variant		ENST00000369318.8	NP_001218.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASP7	ENST00000369318.8	c.-208G>T		upstream_gene_variant		1	NM_001227.5	ENSP00000358324.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.66e-7 AC: 1 AN: 1154560 Hom.: 0 Cov.: 30 AF XY: 0.00000180 AC XY: 1 AN XY: 554522

African (AFR) AF: 0.00 AC: 0 AN: 23890

American (AMR) AF: 0.00 AC: 0 AN: 13708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15944

East Asian (EAS) AF: 0.00 AC: 0 AN: 27780

South Asian (SAS) AF: 0.00 AC: 0 AN: 42806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25986

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3154

European-Non Finnish (NFE) AF: 0.00000105 AC: 1 AN: 954512

Other (OTH) AF: 0.00 AC: 0 AN: 46780

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 596

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	0.30
DANN	Benign	0.54
DEOGEN2	Benign	0.010	T
FATHMM_MKL	Benign	0.00041	N
LIST_S2	Benign	0.35	T
MetaRNN	Benign	0.14	T
PhyloP100		-2.2
PrimateAI	Uncertain	0.57	T
Vest4		0.17
MVP		0.76
GERP RS		-4.4
PromoterAI		-0.025	Neutral
gMVP		0.072
Mutation Taster		=100/0	polymorphism

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: rs28411397; hg19: chr10-115439530;