rs1862710

Positions:

• chr1-15517562-G-A

Variant summary

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

The NM_001229.5(CASP9):​c.418+548C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 152,038 control chromosomes in the GnomAD database, including 33,079 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 0.64 (33079 hom., cov: 32)
• Consequence: CASP9 NM_001229.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48

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]

CASP9 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.844 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASP9	NM_001229.5	c.418+548C>T		intron_variant		ENST00000333868.10	NP_001220.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASP9	ENST00000333868.10	c.418+548C>T		intron_variant		1	NM_001229.5	ENSP00000330237.5

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97880 AN: 151920 Hom.: 33032 Cov.: 32

Gnomad AFR AF: 0.851

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.647

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.563

Gnomad OTH AF: 0.595

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

GnomAD4 genome AF: 0.644 AC: 97975 AN: 152038 Hom.: 33079 Cov.: 32 AF XY: 0.644 AC XY: 47836 AN XY: 74288

Gnomad4 AFR AF: 0.851

Gnomad4 AMR AF: 0.527

Gnomad4 ASJ AF: 0.517

Gnomad4 EAS AF: 0.647

Gnomad4 SAS AF: 0.432

Gnomad4 FIN AF: 0.673

Gnomad4 NFE AF: 0.563

Gnomad4 OTH AF: 0.590

Alfa AF: 0.558 Hom.: 31731

Bravo AF: 0.643

Asia WGS AF: 0.565 AC: 1965 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.15
DANN	Benign	0.67

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: rs1862710; hg19: chr1-15844057;