rs7907519

Positions:

• chr10-113681924-A-C
• chr10-113681924-A-G
• chr10-113681924-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000369318.8(CASP7):​c.-1+1946A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.679 in 152,036 control chromosomes in the GnomAD database, including 36,344 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 0.68 (36344 hom., cov: 31)
• Consequence: CASP7 ENST00000369318.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.855 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASP7	NM_001227.5	c.-1+1946A>C		intron_variant		ENST00000369318.8	NP_001218.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASP7	ENST00000369318.8	c.-1+1946A>C		intron_variant		1	NM_001227.5	ENSP00000358324	P1

Frequencies

GnomAD3 genomes AF: 0.679 AC: 103154 AN: 151918 Hom.: 36288 Cov.: 31

Gnomad AFR AF: 0.862

Gnomad AMI AF: 0.656

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.681

Gnomad EAS AF: 0.764

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.605

Gnomad OTH AF: 0.702

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

GnomAD4 genome AF: 0.679 AC: 103266 AN: 152036 Hom.: 36344 Cov.: 31 AF XY: 0.673 AC XY: 50026 AN XY: 74322

Gnomad4 AFR AF: 0.862

Gnomad4 AMR AF: 0.579

Gnomad4 ASJ AF: 0.681

Gnomad4 EAS AF: 0.764

Gnomad4 SAS AF: 0.651

Gnomad4 FIN AF: 0.550

Gnomad4 NFE AF: 0.605

Gnomad4 OTH AF: 0.704

Alfa AF: 0.599 Hom.: 2392

Bravo AF: 0.687

Asia WGS AF: 0.712 AC: 2475 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.18
DANN	Benign	0.41

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

Publications

LitVar

Other links and lift over

dbSNP: rs7907519; hg19: chr10-115441683;