rs4645980

Variant names:

• chr1-15525181-C-A
• rs4645980
• ENST00000469637.1:c.-239+1010G>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000469637.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASP9	ENST00000469637.1	TSL:3	c.-239+1010G>T		intron	N/A	ENSP00000480785.1	A0A087WX72

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

African (AFR) AF: 0.688 AC: 24647 AN: 35828

American (AMR) AF: 0.483 AC: 6929 AN: 14340

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 1627 AN: 3344

East Asian (EAS) AF: 0.625 AC: 2823 AN: 4516

South Asian (SAS) AF: 0.398 AC: 1739 AN: 4374

European-Finnish (FIN) AF: 0.631 AC: 5758 AN: 9130

Middle Eastern (MID) AF: 0.485 AC: 126 AN: 260

European-Non Finnish (NFE) AF: 0.523 AC: 33774 AN: 64534

Other (OTH) AF: 0.536 AC: 1034 AN: 1930

Alfa AF: 0.371 Hom.: 741

Asia WGS AF: 0.534 AC: 1818 AN: 3404

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.94
DANN	Benign	0.86
PhyloP100		-2.2
PromoterAI		0.023	Neutral

Splicing

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

Other links and lift over

dbSNP: rs4645980; hg19: chr1-15851676;