10-113709866-C-G

Variant names:

• chr10-113709866-C-G
• rs3124740
• NM_001227.5:c.111-11166C>G

Variant summary

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

The NM_001227.5(CASP7):​c.111-11166C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.588 in 152,142 control chromosomes in the GnomAD database, including 27,056 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 0.59 (27056 hom., cov: 33)
• Consequence: CASP7 NM_001227.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0700
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASP7	NM_001227.5	c.111-11166C>G		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.111-11166C>G		intron_variant	Intron 2 of 6	1	NM_001227.5	ENSP00000358324.4

Frequencies

GnomAD3 genomes AF: 0.588 AC: 89382 AN: 152024 Hom.: 27013 Cov.: 33

Gnomad AFR AF: 0.730

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.555

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

GnomAD4 genome AF: 0.588 AC: 89480 AN: 152142 Hom.: 27056 Cov.: 33 AF XY: 0.589 AC XY: 43834 AN XY: 74380

African (AFR) AF: 0.730 AC: 30287 AN: 41488

American (AMR) AF: 0.600 AC: 9177 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.563 AC: 1953 AN: 3470

East Asian (EAS) AF: 0.401 AC: 2074 AN: 5172

South Asian (SAS) AF: 0.534 AC: 2577 AN: 4824

European-Finnish (FIN) AF: 0.591 AC: 6252 AN: 10582

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.521 AC: 35420 AN: 67990

Other (OTH) AF: 0.555 AC: 1174 AN: 2114

Alfa AF: 0.387 Hom.: 920

Bravo AF: 0.597

Asia WGS AF: 0.496 AC: 1727 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.5
DANN	Benign	0.66
PhyloP100		-0.070
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: rs3124740; hg19: chr10-115469625;