rs2288713

chr12-98715645-A-Cchr12-98715645-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181861.2(APAF1):c.3084+93A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0988 in 1,424,444 control chromosomes in the GnomAD database, including 8,218 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 0.084 (723 hom., cov: 31)
  • Exomes 𝑓: 0.10 (7495 hom.)
• Consequence: APAF1 NM_181861.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0580

Genes affected

APAF1 (HGNC:576): (apoptotic peptidase activating factor 1) This gene encodes a cytoplasmic protein that initiates apoptosis. This protein contains several copies of the WD-40 domain, a caspase recruitment domain (CARD), and an ATPase domain (NB-ARC). Upon binding cytochrome c and dATP, this protein forms an oligomeric apoptosome. The apoptosome binds and cleaves caspase 9 preproprotein, releasing its mature, activated form. Activated caspase 9 stimulates the subsequent caspase cascade that commits the cell to apoptosis. Alternative splicing results in several transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APAF1	NM_181861.2	c.3084+93A>C		intron_variant		ENST00000551964.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APAF1	ENST00000551964.6	c.3084+93A>C		intron_variant		1	NM_181861.2	P1

Frequencies

GnomAD3 genomes AF: 0.0843 AC: 12821 AN: 152100 Hom.: 724 Cov.: 31

Gnomad AFR AF: 0.0175

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.0930

Gnomad OTH AF: 0.0879

GnomAD4 exome AF: 0.101 AC: 127932 AN: 1272226 Hom.: 7495 AF XY: 0.104 AC XY: 66865 AN XY: 642624

Gnomad4 AFR exome AF: 0.0150

Gnomad4 AMR exome AF: 0.117

Gnomad4 ASJ exome AF: 0.121

Gnomad4 EAS exome AF: 0.246

Gnomad4 SAS exome AF: 0.189

Gnomad4 FIN exome AF: 0.120

Gnomad4 NFE exome AF: 0.0872

Gnomad4 OTH exome AF: 0.101

GnomAD4 genome AF: 0.0841 AC: 12804 AN: 152218 Hom.: 723 Cov.: 31 AF XY: 0.0889 AC XY: 6619 AN XY: 74418

Gnomad4 AFR AF: 0.0175

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.245

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.117

Gnomad4 NFE AF: 0.0929

Gnomad4 OTH AF: 0.0884

Alfa AF: 0.0969 Hom.: 388

Bravo AF: 0.0788

Asia WGS AF: 0.177 AC: 615 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.6
Dann	Benign	0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs2288713; hg19: chr12-99109423;