rs11196422

Variant names:

• chr10-113683331-G-A
• rs11196422
• NM_001227.5:c.-1+3353G>A

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+3353G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 151,866 control chromosomes in the GnomAD database, including 2,572 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 (2572 hom., cov: 32)
• Consequence: CASP7 NM_001227.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.422
• Publications: 14 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASP7	NM_001227.5	c.-1+3353G>A		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+3353G>A		intron_variant	Intron 1 of 6	1	NM_001227.5	ENSP00000358324.4

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25893 AN: 151748 Hom.: 2569 Cov.: 32

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.0967

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.171 AC: 25929 AN: 151866 Hom.: 2572 Cov.: 32 AF XY: 0.169 AC XY: 12551 AN XY: 74222

African (AFR) AF: 0.266 AC: 11011 AN: 41334

American (AMR) AF: 0.138 AC: 2108 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 789 AN: 3468

East Asian (EAS) AF: 0.156 AC: 808 AN: 5170

South Asian (SAS) AF: 0.164 AC: 788 AN: 4800

European-Finnish (FIN) AF: 0.135 AC: 1428 AN: 10574

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.124 AC: 8440 AN: 67940

Other (OTH) AF: 0.186 AC: 392 AN: 2110

Alfa AF: 0.137 Hom.: 4543

Bravo AF: 0.174

Asia WGS AF: 0.176 AC: 611 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.1
DANN	Benign	0.77
PhyloP100		0.42
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: rs11196422; hg19: chr10-115443090;