NM_001227.5:c.682+417G>A

Variant names:

• chr10-113726851-G-A
• rs6585241
• NM_001227.5:c.682+417G>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.682+417G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.852 in 152,122 control chromosomes in the GnomAD database, including 55,476 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 0.85 (55476 hom., cov: 31)
• Consequence: CASP7 NM_001227.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.570
• Publications: 8 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.914 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASP7	NM_001227.5	c.682+417G>A		intron_variant	Intron 6 of 6	ENST00000369318.8	NP_001218.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASP7	ENST00000369318.8	c.682+417G>A		intron_variant	Intron 6 of 6	1	NM_001227.5	ENSP00000358324.4

Frequencies

GnomAD3 genomes AF: 0.852 AC: 129565 AN: 152004 Hom.: 55431 Cov.: 31

Gnomad AFR AF: 0.922

Gnomad AMI AF: 0.884

Gnomad AMR AF: 0.880

Gnomad ASJ AF: 0.870

Gnomad EAS AF: 0.827

Gnomad SAS AF: 0.841

Gnomad FIN AF: 0.790

Gnomad MID AF: 0.880

Gnomad NFE AF: 0.814

Gnomad OTH AF: 0.862

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

GnomAD4 genome AF: 0.852 AC: 129669 AN: 152122 Hom.: 55476 Cov.: 31 AF XY: 0.851 AC XY: 63277 AN XY: 74354

African (AFR) AF: 0.922 AC: 38294 AN: 41526

American (AMR) AF: 0.880 AC: 13456 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.870 AC: 3020 AN: 3472

East Asian (EAS) AF: 0.827 AC: 4256 AN: 5148

South Asian (SAS) AF: 0.841 AC: 4047 AN: 4812

European-Finnish (FIN) AF: 0.790 AC: 8349 AN: 10566

Middle Eastern (MID) AF: 0.878 AC: 258 AN: 294

European-Non Finnish (NFE) AF: 0.814 AC: 55363 AN: 67994

Other (OTH) AF: 0.861 AC: 1820 AN: 2114

Alfa AF: 0.834 Hom.: 74846

Bravo AF: 0.862

Asia WGS AF: 0.840 AC: 2921 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.14
DANN	Benign	0.37
PhyloP100		-0.57
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: rs6585241; hg19: chr10-115486610;