rs1862710

Variant names:

• chr1-15517562-G-A
• rs1862710
• NM_001229.5:c.418+548C>T

Variant summary

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

The NM_001229.5(CASP9):​c.418+548C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 152,038 control chromosomes in the GnomAD database, including 33,079 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 (33079 hom., cov: 32)
• Consequence: CASP9 NM_001229.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48
• Publications: 14 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=-1.03).
• 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASP9	NM_001229.5	MANE Select	c.418+548C>T		intron	N/A	NP_001220.2
	CASP9	NM_032996.3		c.169+548C>T		intron	N/A	NP_127463.2
	CASP9	NM_001278054.2		c.418+548C>T		intron	N/A	NP_001264983.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASP9	ENST00000333868.10	TSL:1 MANE Select	c.418+548C>T		intron	N/A	ENSP00000330237.5
	CASP9	ENST00000348549.9	TSL:1	c.418+548C>T		intron	N/A	ENSP00000255256.7
	CASP9	ENST00000400777.7	TSL:1	n.409+548C>T		intron	N/A	ENSP00000383588.3

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97880 AN: 151920 Hom.: 33032 Cov.: 32

Gnomad AFR AF: 0.851

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.517

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

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.644 AC: 97975 AN: 152038 Hom.: 33079 Cov.: 32 AF XY: 0.644 AC XY: 47836 AN XY: 74288

African (AFR) AF: 0.851 AC: 35346 AN: 41514

American (AMR) AF: 0.527 AC: 8050 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.517 AC: 1795 AN: 3470

East Asian (EAS) AF: 0.647 AC: 3344 AN: 5170

South Asian (SAS) AF: 0.432 AC: 2078 AN: 4812

European-Finnish (FIN) AF: 0.673 AC: 7096 AN: 10542

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.563 AC: 38267 AN: 67950

Other (OTH) AF: 0.590 AC: 1244 AN: 2108

Alfa AF: 0.568 Hom.: 42126

Bravo AF: 0.643

Asia WGS AF: 0.565 AC: 1965 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.15
DANN	Benign	0.67
PhyloP100		-1.5
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

Other links and lift over

dbSNP: rs1862710; hg19: chr1-15844057;