rs4645980

Positions:

• chr1-15525181-C-A
• chr1-15525181-C-T

Variant summary

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

The ENST00000469637.1(CASP9):​c.-239+1010G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.57 (22917 hom., cov: 19)
• Consequence: CASP9 ENST00000469637.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.19

Genes affected

CASP9 (HGNC:1511): (caspase 9) 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. This protein can undergo autoproteolytic processing and activation by the apoptosome, a protein complex of cytochrome c and the apoptotic peptidase activating factor 1; this step is thought to be one of the earliest in the caspase activation cascade. This protein is thought to play a central role in apoptosis and to be a tumor suppressor. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.681 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASP9	ENST00000469637.1	c.-239+1010G>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.567 AC: 78789 AN: 138994 Hom.: 22882 Cov.: 19

Gnomad AFR AF: 0.687

Gnomad AMI AF: 0.485

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.625

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.539

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

GnomAD4 genome AF: 0.567 AC: 78854 AN: 139074 Hom.: 22917 Cov.: 19 AF XY: 0.568 AC XY: 38392 AN XY: 67644

Gnomad4 AFR AF: 0.688

Gnomad4 AMR AF: 0.483

Gnomad4 ASJ AF: 0.487

Gnomad4 EAS AF: 0.625

Gnomad4 SAS AF: 0.398

Gnomad4 FIN AF: 0.631

Gnomad4 NFE AF: 0.523

Gnomad4 OTH AF: 0.536

Alfa AF: 0.371 Hom.: 741

Asia WGS AF: 0.534 AC: 1818 AN: 3404

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.94
DANN	Benign	0.86

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4645980; hg19: chr1-15851676;