rs11196444

Variant names:

• chr10-113708928-G-C
• rs11196444
• NM_001227.5:c.110+11325G>C

Variant summary

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

The NM_001227.5(CASP7):​c.110+11325G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 151,534 control chromosomes in the GnomAD database, including 2,980 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 0.17 (2980 hom., cov: 32)
• Consequence: CASP7 NM_001227.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0820
• Publications: 2 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001227.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASP7	NM_001227.5	MANE Select	c.110+11325G>C		intron	N/A	NP_001218.1
	CASP7	NM_001267057.1		c.334+11325G>C		intron	N/A	NP_001253986.1
	CASP7	NM_033338.6		c.209+11325G>C		intron	N/A	NP_203124.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASP7	ENST00000369318.8	TSL:1 MANE Select	c.110+11325G>C		intron	N/A	ENSP00000358324.4
	CASP7	ENST00000621607.4	TSL:1	c.209+11325G>C		intron	N/A	ENSP00000478999.1
	CASP7	ENST00000345633.8	TSL:1	c.110+11325G>C		intron	N/A	ENSP00000298701.7

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26440 AN: 151416 Hom.: 2977 Cov.: 32

Gnomad AFR AF: 0.0506

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.0680

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.174 AC: 26442 AN: 151534 Hom.: 2980 Cov.: 32 AF XY: 0.180 AC XY: 13360 AN XY: 74078

African (AFR) AF: 0.0505 AC: 2084 AN: 41248

American (AMR) AF: 0.309 AC: 4709 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 673 AN: 3468

East Asian (EAS) AF: 0.0678 AC: 349 AN: 5148

South Asian (SAS) AF: 0.214 AC: 1022 AN: 4780

European-Finnish (FIN) AF: 0.253 AC: 2674 AN: 10552

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.212 AC: 14338 AN: 67788

Other (OTH) AF: 0.160 AC: 337 AN: 2102

Alfa AF: 0.183 Hom.: 370

Bravo AF: 0.173

Asia WGS AF: 0.138 AC: 478 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.7
DANN	Benign	0.61
PhyloP100		0.082
PromoterAI		0.013	Neutral
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: rs11196444; hg19: chr10-115468687;