rs11196438

Positions:

• chr10-113699222-A-G

Variant summary

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

The ENST00000369318.8(CASP7):​c.110+1619A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0796 in 152,276 control chromosomes in the GnomAD database, including 638 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 0.080 (638 hom., cov: 32)
• Consequence: CASP7 ENST00000369318.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.201

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASP7	NM_001227.5	c.110+1619A>G		intron_variant		ENST00000369318.8	NP_001218.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASP7	ENST00000369318.8	c.110+1619A>G		intron_variant		1	NM_001227.5	ENSP00000358324	P1

Frequencies

GnomAD3 genomes AF: 0.0797 AC: 12131 AN: 152158 Hom.: 638 Cov.: 32

Gnomad AFR AF: 0.0320

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.0503

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.0931

Gnomad SAS AF: 0.0973

Gnomad FIN AF: 0.0750

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.0832

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

GnomAD4 genome AF: 0.0796 AC: 12125 AN: 152276 Hom.: 638 Cov.: 32 AF XY: 0.0780 AC XY: 5806 AN XY: 74464

Gnomad4 AFR AF: 0.0319

Gnomad4 AMR AF: 0.0502

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.0925

Gnomad4 SAS AF: 0.0976

Gnomad4 FIN AF: 0.0750

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.0823

Alfa AF: 0.0914 Hom.: 89

Bravo AF: 0.0760

Asia WGS AF: 0.0870 AC: 301 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	0.41
DANN	Benign	0.72

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: rs11196438; hg19: chr10-115458981;