1-15507665-T-C

Position:

• chr1-15507665-T-C

Variant summary

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

The NM_001229.5(CASP9):​c.453+208A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 576,072 control chromosomes in the GnomAD database, including 89,808 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 (26938 hom., cov: 31)
  • Exomes 𝑓: 0.54 (62870 hom.)
• Consequence: CASP9 NM_001229.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.651

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASP9	NM_001229.5	c.453+208A>G		intron_variant		ENST00000333868.10	NP_001220.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASP9	ENST00000333868.10	c.453+208A>G		intron_variant		1	NM_001229.5	ENSP00000330237.5

Frequencies

GnomAD3 genomes AF: 0.587 AC: 89230 AN: 151884 Hom.: 26899 Cov.: 31

Gnomad AFR AF: 0.709

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.647

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.651

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.538

Gnomad OTH AF: 0.556

GnomAD4 exome AF: 0.538 AC: 228141 AN: 424072 Hom.: 62870 AF XY: 0.532 AC XY: 118804 AN XY: 223510

Gnomad4 AFR exome AF: 0.705

Gnomad4 AMR exome AF: 0.446

Gnomad4 ASJ exome AF: 0.490

Gnomad4 EAS exome AF: 0.642

Gnomad4 SAS exome AF: 0.427

Gnomad4 FIN exome AF: 0.627

Gnomad4 NFE exome AF: 0.534

Gnomad4 OTH exome AF: 0.545

GnomAD4 genome AF: 0.588 AC: 89317 AN: 152000 Hom.: 26938 Cov.: 31 AF XY: 0.588 AC XY: 43698 AN XY: 74320

Gnomad4 AFR AF: 0.709

Gnomad4 AMR AF: 0.498

Gnomad4 ASJ AF: 0.494

Gnomad4 EAS AF: 0.647

Gnomad4 SAS AF: 0.424

Gnomad4 FIN AF: 0.651

Gnomad4 NFE AF: 0.538

Gnomad4 OTH AF: 0.553

Alfa AF: 0.453 Hom.: 1366

Bravo AF: 0.582

Asia WGS AF: 0.553 AC: 1924 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.7
DANN	Benign	0.28

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: rs4646034; hg19: chr1-15834160;