rs4233533

Variant names:

• chr1-15502692-G-A
• rs4233533
• NM_001229.5:c.868+1919C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-15502692-G-A
• chr1-15502692-G-C
• chr1-15502692-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001229.5(CASP9):​c.868+1919C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 152,086 control chromosomes in the GnomAD database, including 6,793 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 0.29 (6793 hom., cov: 32)
• Consequence: CASP9 NM_001229.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.604
• Publications: 16 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASP9	NM_001229.5	c.868+1919C>T		intron_variant	Intron 6 of 8	ENST00000333868.10	NP_001220.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASP9	ENST00000333868.10	c.868+1919C>T		intron_variant	Intron 6 of 8	1	NM_001229.5	ENSP00000330237.5

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43578 AN: 151968 Hom.: 6790 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.571

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.262

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

GnomAD4 genome AF: 0.287 AC: 43587 AN: 152086 Hom.: 6793 Cov.: 32 AF XY: 0.290 AC XY: 21593 AN XY: 74354

African (AFR) AF: 0.202 AC: 8379 AN: 41488

American (AMR) AF: 0.298 AC: 4560 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 829 AN: 3468

East Asian (EAS) AF: 0.571 AC: 2945 AN: 5158

South Asian (SAS) AF: 0.243 AC: 1176 AN: 4830

European-Finnish (FIN) AF: 0.369 AC: 3901 AN: 10568

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.307 AC: 20865 AN: 67974

Other (OTH) AF: 0.262 AC: 553 AN: 2112

Alfa AF: 0.281 Hom.: 8057

Bravo AF: 0.278

Asia WGS AF: 0.383 AC: 1332 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.2
DANN	Benign	0.75
PhyloP100		0.60
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: rs4233533; hg19: chr1-15829187;