1-15524569-ATCCCCGCACTGACCTCACG-ATCCCCGCACTGACCTCACGTCCCCGCACTGACCTCACGTCCCCGCACTGACCTCACG

Variant names:

• chr1-15524569-A-ATCCCCGCACTGACCTCACGTCCCCGCACTGACCTCACG
• rs4645982
• NM_032996.3:c.-118+13_-118+14insCGTGAGGTCAGTGCGGGGACGTGAGGTCAGTGCGGGGA

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_032996.3(CASP9):​c.-118+13_-118+14insCGTGAGGTCAGTGCGGGGACGTGAGGTCAGTGCGGGGA 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 0.000039 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000018 (1 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 Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASP9	NM_032996.3	c.-118+13_-118+14insCGTGAGGTCAGTGCGGGGACGTGAGGTCAGTGCGGGGA		intron_variant	Intron 1 of 8		NP_127463.2
CASP9	XM_005246014.3	c.-118+282_-118+283insCGTGAGGTCAGTGCGGGGACGTGAGGTCAGTGCGGGGA		intron_variant	Intron 1 of 8		XP_005246071.1
CASP9	XM_047432034.1	c.-281+282_-281+283insCGTGAGGTCAGTGCGGGGACGTGAGGTCAGTGCGGGGA		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+14insCGTGAGGTCAGTGCGGGGACGTGAGGTCAGTGCGGGGA		intron_variant	Intron 1 of 8	2		ENSP00000365051.4
CASP9	ENST00000447522.5	c.-118+282_-118+283insCGTGAGGTCAGTGCGGGGACGTGAGGTCAGTGCGGGGA		intron_variant	Intron 1 of 6	3		ENSP00000396540.1
CASP9	ENST00000469637.1	c.-239+1621_-239+1622insCGTGAGGTCAGTGCGGGGACGTGAGGTCAGTGCGGGGA		intron_variant	Intron 1 of 2	3		ENSP00000480785.1

Frequencies

GnomAD3 genomes AF: 0.0000386 AC: 2 AN: 51810 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000911

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000215

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000177 AC: 5 AN: 282546 Hom.: 1 Cov.: 8 AF XY: 0.00 AC XY: 0 AN XY: 138688

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000859

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000397

Gnomad4 NFE exome AF: 0.00000423

Gnomad4 OTH exome AF: 0.0000937

GnomAD4 genome AF: 0.0000386 AC: 2 AN: 51814 Hom.: 0 Cov.: 0 AF XY: 0.0000840 AC XY: 2 AN XY: 23810

Gnomad4 AFR AF: 0.0000908

Gnomad4 AMR AF: 0.000215

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

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;