rs4645981

Variant names:

• chr1-15524988-G-A
• rs4645981
• ENST00000469637.1:c.-239+1203C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-15524988-G-A
• chr1-15524988-G-C

Variant summary

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

The ENST00000469637.1(CASP9):​c.-239+1203C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00823 in 105,452 control chromosomes in the GnomAD database, including 41 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 0.0083 (41 hom., cov: 21)
  • Exomes 𝑓: 0.0022 (0 hom.)
• Consequence: CASP9 ENST00000469637.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.154
• Publications: 28 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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000469637.1. 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_032996.3		c.-523C>T		upstream_gene	N/A	NP_127463.2	P55211-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASP9	ENST00000469637.1	TSL:3	c.-239+1203C>T		intron	N/A	ENSP00000480785.1	A0A087WX72
	CASP9	ENST00000447522.5	TSL:3	c.-254C>T		upstream_gene	N/A	ENSP00000396540.1	Q5JRU2

Frequencies

GnomAD3 genomes AF: 0.00834 AC: 864 AN: 103580 Hom.: 41 Cov.: 21

Gnomad AFR AF: 0.000564

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0203

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.00558

Gnomad FIN AF: 0.0193

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000619

Gnomad OTH AF: 0.00797

GnomAD4 exome AF: 0.00218 AC: 4 AN: 1836 Hom.: 0 AF XY: 0.00347 AC XY: 4 AN XY: 1154

African (AFR) AF: 0.00 AC: 0 AN: 22

American (AMR) AF: 0.00 AC: 0 AN: 4

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8

East Asian (EAS) AF: 0.00 AC: 0 AN: 6

South Asian (SAS) AF: 0.00509 AC: 4 AN: 786

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 14

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 942

Other (OTH) AF: 0.00 AC: 0 AN: 50

GnomAD4 genome AF: 0.00834 AC: 864 AN: 103616 Hom.: 41 Cov.: 21 AF XY: 0.00966 AC XY: 464 AN XY: 48056

African (AFR) AF: 0.000563 AC: 15 AN: 26656

American (AMR) AF: 0.0201 AC: 163 AN: 8094

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2840

East Asian (EAS) AF: 0.164 AC: 538 AN: 3280

South Asian (SAS) AF: 0.00632 AC: 17 AN: 2690

European-Finnish (FIN) AF: 0.0193 AC: 87 AN: 4500

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 146

European-Non Finnish (NFE) AF: 0.000619 AC: 33 AN: 53308

Other (OTH) AF: 0.00795 AC: 11 AN: 1384

Alfa AF: 0.00201 Hom.: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.4
DANN	Benign	0.63
PhyloP100		-0.15
PromoterAI		0.037	Neutral

Splicing

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

Other links and lift over

dbSNP: rs4645981; hg19: chr1-15851483;