rs884363

Variant names:

• chr1-15493273-C-A
• rs884363
• NM_001229.5:c.1159-238G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-15493273-C-A
• chr1-15493273-C-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001229.5(CASP9):​c.1159-238G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 1,379,242 control chromosomes in the GnomAD database, including 230,435 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 (33085 hom., cov: 33)
  • Exomes 𝑓: 0.56 (197350 hom.)
• Consequence: CASP9 NM_001229.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.787
• Publications: 5 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: Benign. The variant received -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 = 0.844 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001229.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASP9	NM_001229.5	MANE Select	c.1159-238G>T		intron	N/A	NP_001220.2
	CASP9	NM_032996.3		c.910-238G>T		intron	N/A	NP_127463.2	P55211-4
	CASP9	NM_001278054.2		c.709-238G>T		intron	N/A	NP_001264983.1	P55211-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASP9	ENST00000333868.10	TSL:1 MANE Select	c.1159-238G>T		intron	N/A	ENSP00000330237.5	P55211-1
	CASP9	ENST00000348549.9	TSL:1	c.709-238G>T		intron	N/A	ENSP00000255256.7	P55211-2
	CASP9	ENST00000400777.7	TSL:1	n.*752-238G>T		intron	N/A	ENSP00000383588.3	H0Y3S8

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97925 AN: 152034 Hom.: 33039 Cov.: 33

Gnomad AFR AF: 0.851

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.511

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

GnomAD4 exome AF: 0.563 AC: 691188 AN: 1227090 Hom.: 197350 Cov.: 34 AF XY: 0.560 AC XY: 331943 AN XY: 592242

African (AFR) AF: 0.860 AC: 23170 AN: 26930

American (AMR) AF: 0.481 AC: 7542 AN: 15694

Ashkenazi Jewish (ASJ) AF: 0.514 AC: 8954 AN: 17430

East Asian (EAS) AF: 0.650 AC: 20273 AN: 31212

South Asian (SAS) AF: 0.447 AC: 23449 AN: 52486

European-Finnish (FIN) AF: 0.661 AC: 17625 AN: 26684

Middle Eastern (MID) AF: 0.523 AC: 1764 AN: 3374

European-Non Finnish (NFE) AF: 0.558 AC: 559752 AN: 1002964

Other (OTH) AF: 0.570 AC: 28659 AN: 50316

GnomAD4 genome AF: 0.644 AC: 98020 AN: 152152 Hom.: 33085 Cov.: 33 AF XY: 0.644 AC XY: 47884 AN XY: 74392

African (AFR) AF: 0.852 AC: 35368 AN: 41534

American (AMR) AF: 0.528 AC: 8065 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.511 AC: 1774 AN: 3472

East Asian (EAS) AF: 0.647 AC: 3345 AN: 5172

South Asian (SAS) AF: 0.431 AC: 2082 AN: 4830

European-Finnish (FIN) AF: 0.673 AC: 7117 AN: 10572

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.563 AC: 38265 AN: 67976

Other (OTH) AF: 0.591 AC: 1249 AN: 2114

Alfa AF: 0.615 Hom.: 3850

Bravo AF: 0.643

Asia WGS AF: 0.568 AC: 1973 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.22
DANN	Benign	0.39
PhyloP100		-0.79
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs884363;

hg19: chr1-15819768;