chr10-113680160-G-T

Position:

• chr10-113680160-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001227.5(CASP7):​c.-1+182G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 152,034 control chromosomes in the GnomAD database, including 41,014 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 0.72 (41014 hom., cov: 31)
• Consequence: CASP7 NM_001227.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.586

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.896 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASP7	NM_001227.5	c.-1+182G>T		intron_variant		ENST00000369318.8	NP_001218.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASP7	ENST00000369318.8	c.-1+182G>T		intron_variant		1	NM_001227.5	ENSP00000358324	P1

Frequencies

GnomAD3 genomes AF: 0.723 AC: 109906 AN: 151916 Hom.: 40955 Cov.: 31

Gnomad AFR AF: 0.903

Gnomad AMI AF: 0.686

Gnomad AMR AF: 0.598

Gnomad ASJ AF: 0.721

Gnomad EAS AF: 0.764

Gnomad SAS AF: 0.749

Gnomad FIN AF: 0.639

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.651

Gnomad OTH AF: 0.733

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

GnomAD4 genome AF: 0.724 AC: 110021 AN: 152034 Hom.: 41014 Cov.: 31 AF XY: 0.721 AC XY: 53542 AN XY: 74304

Gnomad4 AFR AF: 0.903

Gnomad4 AMR AF: 0.598

Gnomad4 ASJ AF: 0.721

Gnomad4 EAS AF: 0.764

Gnomad4 SAS AF: 0.751

Gnomad4 FIN AF: 0.639

Gnomad4 NFE AF: 0.651

Gnomad4 OTH AF: 0.734

Alfa AF: 0.582 Hom.: 1727

Bravo AF: 0.725

Asia WGS AF: 0.744 AC: 2586 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.7
DANN	Benign	0.31

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

Publications

LitVar

Other links and lift over

dbSNP: rs7922608; hg19: chr10-115439919;