rs2020903

Variant names:

• chr1-15507802-G-A
• rs2020903
• NM_001229.5:c.453+71C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-15507802-G-A
• chr1-15507802-G-C

Variant summary

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

The NM_001229.5(CASP9):​c.453+71C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 1,485,308 control chromosomes in the GnomAD database, including 218,191 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 0.59 (26824 hom., cov: 32)
  • Exomes 𝑓: 0.53 (191367 hom.)
• Consequence: CASP9 NM_001229.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.689
• Publications: 9 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.699 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.453+71C>T		intron	N/A	NP_001220.2
	CASP9	NM_032996.3		c.204+71C>T		intron	N/A	NP_127463.2	P55211-4
	CASP9	NM_001278054.2		c.418+10308C>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.453+71C>T		intron	N/A	ENSP00000330237.5	P55211-1
	CASP9	ENST00000348549.9	TSL:1	c.418+10308C>T		intron	N/A	ENSP00000255256.7	P55211-2
	CASP9	ENST00000400777.7	TSL:1	n.444+71C>T		intron	N/A	ENSP00000383588.3	H0Y3S8

Frequencies

GnomAD3 genomes AF: 0.586 AC: 89086 AN: 151912 Hom.: 26783 Cov.: 32

Gnomad AFR AF: 0.705

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.647

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.650

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.538

Gnomad OTH AF: 0.555

GnomAD4 exome AF: 0.532 AC: 709049 AN: 1333276 Hom.: 191367 Cov.: 19 AF XY: 0.529 AC XY: 354294 AN XY: 669712

African (AFR) AF: 0.703 AC: 21827 AN: 31040

American (AMR) AF: 0.418 AC: 18453 AN: 44106

Ashkenazi Jewish (ASJ) AF: 0.492 AC: 12304 AN: 25006

East Asian (EAS) AF: 0.644 AC: 25167 AN: 39076

South Asian (SAS) AF: 0.432 AC: 35967 AN: 83260

European-Finnish (FIN) AF: 0.638 AC: 33754 AN: 52906

Middle Eastern (MID) AF: 0.500 AC: 2418 AN: 4838

European-Non Finnish (NFE) AF: 0.531 AC: 528977 AN: 997022

Other (OTH) AF: 0.539 AC: 30182 AN: 56022

GnomAD4 genome AF: 0.587 AC: 89176 AN: 152032 Hom.: 26824 Cov.: 32 AF XY: 0.587 AC XY: 43642 AN XY: 74324

African (AFR) AF: 0.706 AC: 29245 AN: 41450

American (AMR) AF: 0.498 AC: 7615 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.494 AC: 1713 AN: 3470

East Asian (EAS) AF: 0.647 AC: 3346 AN: 5170

South Asian (SAS) AF: 0.424 AC: 2044 AN: 4818

European-Finnish (FIN) AF: 0.650 AC: 6873 AN: 10566

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.538 AC: 36550 AN: 67958

Other (OTH) AF: 0.552 AC: 1167 AN: 2114

Alfa AF: 0.567 Hom.: 3223

Bravo AF: 0.581

Asia WGS AF: 0.553 AC: 1924 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.7
DANN	Benign	0.62
PhyloP100		0.69
Mutation Taster		=11/89	disease causing

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: rs2020903; hg19: chr1-15834297; COSMIC: COSV61601098; COSMIC: COSV61601098;