18-23135987-C-T
Position:
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2
The NM_001100619.3(CABLES1):c.225C>T(p.Asp75=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00214 in 1,138,040 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0014 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0022 ( 4 hom. )
Consequence
CABLES1
NM_001100619.3 synonymous
NM_001100619.3 synonymous
Scores
1
1
Clinical Significance
Conservation
PhyloP100: 0.481
Genes affected
CABLES1 (HGNC:25097): (Cdk5 and Abl enzyme substrate 1) This gene encodes a protein involved in regulation of the cell cycle through interactions with several cyclin-dependent kinases. One study (PMID: 16177568) reported aberrant splicing of transcripts from this gene which results in removal of the cyclin binding domain only in human cancer cells, and reduction in gene expression was shown in colorectal cancers (PMID: 17982127).Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.33).
BP6
Variant 18-23135987-C-T is Benign according to our data. Variant chr18-23135987-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 779177.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.481 with no splicing effect.
BS2
High Homozygotes in GnomAdExome4 at 4 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CABLES1 | NM_001100619.3 | c.225C>T | p.Asp75= | synonymous_variant | 1/10 | ENST00000256925.12 | |
CABLES1 | NM_001256438.1 | c.-137+1317C>T | intron_variant | ||||
CABLES1 | NR_023359.2 | n.88+1336C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CABLES1 | ENST00000256925.12 | c.225C>T | p.Asp75= | synonymous_variant | 1/10 | 1 | NM_001100619.3 | ||
CABLES1 | ENST00000400473.6 | c.-137+1317C>T | intron_variant | 2 | P1 | ||||
CABLES1 | ENST00000580153.5 | c.-221+442C>T | intron_variant | 5 | |||||
CABLES1 | ENST00000579963.5 | c.-137+1336C>T | intron_variant, NMD_transcript_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.00143 AC: 212AN: 148268Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
212
AN:
148268
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00199 AC: 54AN: 27112Hom.: 0 AF XY: 0.00265 AC XY: 41AN XY: 15482
GnomAD3 exomes
AF:
AC:
54
AN:
27112
Hom.:
AF XY:
AC XY:
41
AN XY:
15482
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00225 AC: 2225AN: 989664Hom.: 4 Cov.: 30 AF XY: 0.00233 AC XY: 1090AN XY: 468616
GnomAD4 exome
AF:
AC:
2225
AN:
989664
Hom.:
Cov.:
30
AF XY:
AC XY:
1090
AN XY:
468616
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.00143 AC: 212AN: 148376Hom.: 0 Cov.: 32 AF XY: 0.00116 AC XY: 84AN XY: 72298
GnomAD4 genome
AF:
AC:
212
AN:
148376
Hom.:
Cov.:
32
AF XY:
AC XY:
84
AN XY:
72298
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at