chr10-113710131-G-A

Variant names:

• chr10-113710131-G-A
• rs11196445
• NM_001227.5:c.111-10901G>A

Variant summary

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

The NM_001267057.1(CASP7):​c.335-10870G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,196 control chromosomes in the GnomAD database, including 1,094 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 0.11 (1094 hom., cov: 33)
• Consequence: CASP7 NM_001267057.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.486
• Publications: 5 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001267057.1. 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.111-10901G>A		intron	N/A	NP_001218.1
	CASP7	NM_001267057.1		c.335-10870G>A		intron	N/A	NP_001253986.1
	CASP7	NM_033338.6		c.210-10901G>A		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.111-10901G>A		intron	N/A	ENSP00000358324.4
	CASP7	ENST00000621607.4	TSL:1	c.210-10901G>A		intron	N/A	ENSP00000478999.1
	CASP7	ENST00000345633.8	TSL:1	c.111-10901G>A		intron	N/A	ENSP00000298701.7

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17269 AN: 152078 Hom.: 1092 Cov.: 33

Gnomad AFR AF: 0.0774

Gnomad AMI AF: 0.0967

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.144

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

GnomAD4 genome AF: 0.114 AC: 17275 AN: 152196 Hom.: 1094 Cov.: 33 AF XY: 0.114 AC XY: 8493 AN XY: 74400

African (AFR) AF: 0.0772 AC: 3206 AN: 41544

American (AMR) AF: 0.111 AC: 1701 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 710 AN: 3470

East Asian (EAS) AF: 0.158 AC: 817 AN: 5182

South Asian (SAS) AF: 0.156 AC: 752 AN: 4818

European-Finnish (FIN) AF: 0.134 AC: 1421 AN: 10580

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8211 AN: 68000

Other (OTH) AF: 0.145 AC: 306 AN: 2110

Alfa AF: 0.121 Hom.: 1770

Bravo AF: 0.110

Asia WGS AF: 0.160 AC: 557 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.20
DANN	Benign	0.57
PhyloP100		-0.49
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: rs11196445; hg19: chr10-115469890;