1-15525539-C-T

Position:

• chr1-15525539-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+652G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 147,324 control chromosomes in the GnomAD database, including 26,136 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 0.59 (26136 hom., cov: 24)
• Consequence: CASP9 ENST00000469637.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.280

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=-0.6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASP9	ENST00000469637.1	c.-239+652G>A		intron_variant		3		ENSP00000480785.1

Frequencies

GnomAD3 genomes AF: 0.586 AC: 86220 AN: 147224 Hom.: 26100 Cov.: 24

Gnomad AFR AF: 0.707

Gnomad AMI AF: 0.513

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.650

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.653

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.537

Gnomad OTH AF: 0.556

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

GnomAD4 genome AF: 0.586 AC: 86294 AN: 147324 Hom.: 26136 Cov.: 24 AF XY: 0.586 AC XY: 41874 AN XY: 71494

Gnomad4 AFR AF: 0.707

Gnomad4 AMR AF: 0.496

Gnomad4 ASJ AF: 0.501

Gnomad4 EAS AF: 0.650

Gnomad4 SAS AF: 0.421

Gnomad4 FIN AF: 0.653

Gnomad4 NFE AF: 0.537

Gnomad4 OTH AF: 0.552

Alfa AF: 0.556 Hom.: 2913

Bravo AF: 0.580

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	4.3
DANN	Benign	0.91

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4645978; hg19: chr1-15852034;