chr10-113724247-C-T

Variant names:

• chr10-113724247-C-T
• rs12359418
• NM_001227.5:c.377-1115C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001227.5(CASP7):​c.377-1115C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0853 in 152,212 control chromosomes in the GnomAD database, including 680 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 0.085 (680 hom., cov: 32)
• Consequence: CASP7 NM_001227.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.331
• Publications: 1 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASP7	NM_001227.5	c.377-1115C>T		intron_variant	Intron 4 of 6	ENST00000369318.8	NP_001218.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASP7	ENST00000369318.8	c.377-1115C>T		intron_variant	Intron 4 of 6	1	NM_001227.5	ENSP00000358324.4

Frequencies

GnomAD3 genomes AF: 0.0853 AC: 12981 AN: 152094 Hom.: 680 Cov.: 32

Gnomad AFR AF: 0.0482

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.0522

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.0832

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.0744

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.0909

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0853 AC: 12977 AN: 152212 Hom.: 680 Cov.: 32 AF XY: 0.0840 AC XY: 6248 AN XY: 74414

African (AFR) AF: 0.0481 AC: 1998 AN: 41536

American (AMR) AF: 0.0522 AC: 798 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 478 AN: 3470

East Asian (EAS) AF: 0.0826 AC: 427 AN: 5168

South Asian (SAS) AF: 0.126 AC: 607 AN: 4824

European-Finnish (FIN) AF: 0.0744 AC: 788 AN: 10590

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.112 AC: 7599 AN: 68006

Other (OTH) AF: 0.0900 AC: 190 AN: 2112

Alfa AF: 0.101 Hom.: 166

Bravo AF: 0.0814

Asia WGS AF: 0.100 AC: 349 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.94
PhyloP100		-0.33
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: rs12359418; hg19: chr10-115484006;