1-15494112-A-T

Variant names:

• chr1-15494112-A-T
• rs2020895
• NM_001229.5:c.1049-111T>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001229.5(CASP9):​c.1049-111T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.0 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CASP9 NM_001229.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70
• Publications: 6 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASP9	NM_001229.5	c.1049-111T>A		intron_variant	Intron 7 of 8	ENST00000333868.10	NP_001220.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASP9	ENST00000333868.10	c.1049-111T>A		intron_variant	Intron 7 of 8	1	NM_001229.5	ENSP00000330237.5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 151842 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: AC0 AF: 0.00 AC: 0 AN: 1188778 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 588964

African (AFR) AF: 0.00 AC: 0 AN: 27940

American (AMR) AF: 0.00 AC: 0 AN: 32938

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21394

East Asian (EAS) AF: 0.00 AC: 0 AN: 34656

South Asian (SAS) AF: 0.00 AC: 0 AN: 69404

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32762

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3836

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 914774

Other (OTH) AF: 0.00 AC: 0 AN: 51074

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 151842 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74136

African (AFR) AF: 0.00 AC: 0 AN: 41338

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10554

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67932

Other (OTH) AF: 0.00 AC: 0 AN: 2082

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.077
DANN	Benign	0.53
PhyloP100		-1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2020895; hg19: chr1-15820607;