rs2020903

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.689
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CASP9NM_001229.5 linkuse as main transcriptc.453+71C>T intron_variant ENST00000333868.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CASP9ENST00000333868.10 linkuse as main transcriptc.453+71C>T intron_variant 1 NM_001229.5 P1P55211-1

Frequencies

GnomAD3 genomes
AF:
0.586
AC:
89086
AN:
151912
Hom.:
26783
Cov.:
32
show subpopulations
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
show subpopulations
Gnomad4 AFR exome
AF:
0.703
Gnomad4 AMR exome
AF:
0.418
Gnomad4 ASJ exome
AF:
0.492
Gnomad4 EAS exome
AF:
0.644
Gnomad4 SAS exome
AF:
0.432
Gnomad4 FIN exome
AF:
0.638
Gnomad4 NFE exome
AF:
0.531
Gnomad4 OTH exome
AF:
0.539
GnomAD4 genome
AF:
0.587
AC:
89176
AN:
152032
Hom.:
26824
Cov.:
32
AF XY:
0.587
AC XY:
43642
AN XY:
74324
show subpopulations
Gnomad4 AFR
AF:
0.706
Gnomad4 AMR
AF:
0.498
Gnomad4 ASJ
AF:
0.494
Gnomad4 EAS
AF:
0.647
Gnomad4 SAS
AF:
0.424
Gnomad4 FIN
AF:
0.650
Gnomad4 NFE
AF:
0.538
Gnomad4 OTH
AF:
0.552
Alfa
AF:
0.563
Hom.:
3061
Bravo
AF:
0.581
Asia WGS
AF:
0.553
AC:
1924
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
8.7
DANN
Benign
0.62

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

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