NM_001227.5:c.111-4653C>T

Variant names:

• chr10-113716379-C-T
• rs17090904
• NM_001227.5:c.111-4653C>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.111-4653C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 151,726 control chromosomes in the GnomAD database, including 11,029 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 0.38 (11029 hom., cov: 30)
• Consequence: CASP7 NM_001227.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 7 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]

ENSG00000234393 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASP7	NM_001227.5	c.111-4653C>T		intron_variant	Intron 2 of 6	ENST00000369318.8	NP_001218.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASP7	ENST00000369318.8	c.111-4653C>T		intron_variant	Intron 2 of 6	1	NM_001227.5	ENSP00000358324.4

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57260 AN: 151608 Hom.: 11013 Cov.: 30

Gnomad AFR AF: 0.401

Gnomad AMI AF: 0.474

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.502

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.368

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

GnomAD4 genome AF: 0.378 AC: 57319 AN: 151726 Hom.: 11029 Cov.: 30 AF XY: 0.376 AC XY: 27877 AN XY: 74124

African (AFR) AF: 0.402 AC: 16603 AN: 41332

American (AMR) AF: 0.326 AC: 4983 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 1101 AN: 3460

East Asian (EAS) AF: 0.501 AC: 2569 AN: 5126

South Asian (SAS) AF: 0.372 AC: 1783 AN: 4798

European-Finnish (FIN) AF: 0.346 AC: 3639 AN: 10524

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.373 AC: 25328 AN: 67908

Other (OTH) AF: 0.369 AC: 779 AN: 2110

Alfa AF: 0.379 Hom.: 3964

Bravo AF: 0.379

Asia WGS AF: 0.408 AC: 1413 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.60
DANN	Benign	0.79
PhyloP100		-1.1
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: rs17090904; hg19: chr10-115476138;