NM_001227.5:c.110+1619A>G

Variant names:

• chr10-113699222-A-G
• rs11196438
• NM_001227.5:c.110+1619A>G

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+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 NM_001227.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.201
• Publications: 1 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=-0.9).
• 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 rank	MANE	Protein	UniProt
CASP7	NM_001227.5	c.110+1619A>G		intron_variant	Intron 2 of 6	ENST00000369318.8	NP_001218.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASP7	ENST00000369318.8	c.110+1619A>G		intron_variant	Intron 2 of 6	1	NM_001227.5	ENSP00000358324.4

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

African (AFR) AF: 0.0319 AC: 1326 AN: 41544

American (AMR) AF: 0.0502 AC: 768 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 459 AN: 3470

East Asian (EAS) AF: 0.0925 AC: 479 AN: 5176

South Asian (SAS) AF: 0.0976 AC: 471 AN: 4826

European-Finnish (FIN) AF: 0.0750 AC: 797 AN: 10622

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7566 AN: 68018

Other (OTH) AF: 0.0823 AC: 174 AN: 2114

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
PhyloP100		-0.20
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: rs11196438; hg19: chr10-115458981;