10-113690755-C-G

Variant names:

• chr10-113690755-C-G
• rs4342983
• NM_001227.5:c.1-6739C>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.1-6739C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.942 in 152,264 control chromosomes in the GnomAD database, including 67,683 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 0.94 (67683 hom., cov: 32)
• Consequence: CASP7 NM_001227.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.798
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.979 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASP7	NM_001227.5	c.1-6739C>G		intron_variant	Intron 1 of 6	ENST00000369318.8	NP_001218.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASP7	ENST00000369318.8	c.1-6739C>G		intron_variant	Intron 1 of 6	1	NM_001227.5	ENSP00000358324.4

Frequencies

GnomAD3 genomes AF: 0.942 AC: 143323 AN: 152146 Hom.: 67623 Cov.: 32

Gnomad AFR AF: 0.987

Gnomad AMI AF: 0.998

Gnomad AMR AF: 0.956

Gnomad ASJ AF: 0.952

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.955

Gnomad FIN AF: 0.885

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.914

Gnomad OTH AF: 0.946

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

GnomAD4 genome AF: 0.942 AC: 143442 AN: 152264 Hom.: 67683 Cov.: 32 AF XY: 0.942 AC XY: 70105 AN XY: 74432

African (AFR) AF: 0.987 AC: 41002 AN: 41560

American (AMR) AF: 0.956 AC: 14625 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.952 AC: 3302 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5178 AN: 5180

South Asian (SAS) AF: 0.955 AC: 4599 AN: 4814

European-Finnish (FIN) AF: 0.885 AC: 9374 AN: 10594

Middle Eastern (MID) AF: 0.986 AC: 290 AN: 294

European-Non Finnish (NFE) AF: 0.914 AC: 62158 AN: 68022

Other (OTH) AF: 0.947 AC: 2004 AN: 2116

Alfa AF: 0.909 Hom.: 2977

Bravo AF: 0.948

Asia WGS AF: 0.987 AC: 3432 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.70
PhyloP100		-0.80
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: rs4342983; hg19: chr10-115450514;