1-15524569-ATCCCCGCACTGACCTCACG-ATCCCCGCACTGACCTCACGTCCCCGCACTGACCTCACG

Variant names:

• chr1-15524569-A-ATCCCCGCACTGACCTCACG
• rs4645982
• NM_032996.3:c.-123_-118+13dupCGTGAGGTCAGTGCGGGGA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_032996.3(CASP9):​c.-123_-118+13dupCGTGAGGTCAGTGCGGGGA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.51 (5867 hom., cov: 0)
  • Exomes 𝑓: 0.52 (45072 hom.)
  • Failed GnomAD Quality Control
• Consequence: CASP9 NM_032996.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.490

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASP9	NM_032996.3	c.-123_-118+13dupCGTGAGGTCAGTGCGGGGA		intron_variant	Intron 1 of 8		NP_127463.2
CASP9	XM_005246014.3	c.-118+264_-118+282dupCGTGAGGTCAGTGCGGGGA		intron_variant	Intron 1 of 8		XP_005246071.1
CASP9	XM_047432034.1	c.-281+264_-281+282dupCGTGAGGTCAGTGCGGGGA		intron_variant	Intron 1 of 7		XP_047287990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASP9	ENST00000375890.8	c.-118+13_-118+14insCGTGAGGTCAGTGCGGGGA		intron_variant	Intron 1 of 8	2		ENSP00000365051.4
CASP9	ENST00000447522.5	c.-118+282_-118+283insCGTGAGGTCAGTGCGGGGA		intron_variant	Intron 1 of 6	3		ENSP00000396540.1
CASP9	ENST00000469637.1	c.-239+1621_-239+1622insCGTGAGGTCAGTGCGGGGA		intron_variant	Intron 1 of 2	3		ENSP00000480785.1

Frequencies

GnomAD3 genomes AF: 0.506 AC: 25666 AN: 50690 Hom.: 5861 Cov.: 0

Gnomad AFR AF: 0.617

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.442

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.571

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.463

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.521 AC: 146359 AN: 281060 Hom.: 45072 Cov.: 8 AF XY: 0.514 AC XY: 70902 AN XY: 138022

Gnomad4 AFR exome AF: 0.734

Gnomad4 AMR exome AF: 0.394

Gnomad4 ASJ exome AF: 0.418

Gnomad4 EAS exome AF: 0.609

Gnomad4 SAS exome AF: 0.370

Gnomad4 FIN exome AF: 0.557

Gnomad4 NFE exome AF: 0.531

Gnomad4 OTH exome AF: 0.511

GnomAD4 genome AF: 0.506 AC: 25672 AN: 50690 Hom.: 5867 Cov.: 0 AF XY: 0.510 AC XY: 11899 AN XY: 23322

Gnomad4 AFR AF: 0.617

Gnomad4 AMR AF: 0.465

Gnomad4 ASJ AF: 0.442

Gnomad4 EAS AF: 0.559

Gnomad4 SAS AF: 0.335

Gnomad4 FIN AF: 0.571

Gnomad4 NFE AF: 0.477

Gnomad4 OTH AF: 0.465

Alfa AF: 0.342 Hom.: 843

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4645982; hg19: chr1-15851064;