18-23136294-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001100619.3(CABLES1):c.532G>A(p.Glu178Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00919 in 1,389,104 control chromosomes in the GnomAD database, including 86 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0068 ( 11 hom., cov: 33)

Exomes 𝑓: 0.0095 ( 75 hom. )

Consequence

CABLES1
NM_001100619.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.15

Variant links:

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]

CABLES1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0034505427).

BP6

Variant 18-23136294-G-A is Benign according to our data. Variant chr18-23136294-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2648619.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CABLES1	NM_001100619.3 linkuse as main transcript	c.532G>A	p.Glu178Lys	missense_variant	1/10	ENST00000256925.12
CABLES1	NM_001256438.1 linkuse as main transcript	c.-137+1624G>A		intron_variant
CABLES1	NR_023359.2 linkuse as main transcript	n.88+1643G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CABLES1	ENST00000256925.12 linkuse as main transcript	c.532G>A	p.Glu178Lys	missense_variant	1/10	1	NM_001100619.3		Q8TDN4-1
CABLES1	ENST00000400473.6 linkuse as main transcript	c.-137+1624G>A		intron_variant		2		P1	Q8TDN4-4
CABLES1	ENST00000580153.5 linkuse as main transcript	c.-220-230G>A		intron_variant		5
CABLES1	ENST00000579963.5 linkuse as main transcript	c.-137+1643G>A		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00683

AC:

1036

AN:

151618

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00160

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00413

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00684

Gnomad FIN

AF:

0.0190

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00964

Gnomad OTH

AF:

0.00337

GnomAD3 exomes

AF:

0.0138

AC:

224

AN:

16268

Hom.:

AF XY:

0.0131

AC XY:

122

AN XY:

9282

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00579

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00351

Gnomad FIN exome

AF:

0.0217

Gnomad NFE exome

AF:

0.00966

Gnomad OTH exome

AF:

0.00714

GnomAD4 exome

AF:

0.00948

AC:

11725

AN:

1237376

Hom.:

Cov.:

AF XY:

0.00927

AC XY:

5604

AN XY:

604302

show subpopulations

Gnomad4 AFR exome

AF:

0.00139

Gnomad4 AMR exome

AF:

0.00195

Gnomad4 ASJ exome

AF:

0.00483

Gnomad4 EAS exome

AF:

0.0000361

Gnomad4 SAS exome

AF:

0.00419

Gnomad4 FIN exome

AF:

0.0178

Gnomad4 NFE exome

AF:

0.0102

Gnomad4 OTH exome

AF:

0.00688

GnomAD4 genome

AF:

0.00682

AC:

1035

AN:

151728

Hom.:

Cov.:

AF XY:

0.00744

AC XY:

552

AN XY:

74154

show subpopulations

Gnomad4 AFR

AF:

0.00159

Gnomad4 AMR

AF:

0.00413

Gnomad4 ASJ

AF:

0.00375

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00684

Gnomad4 FIN

AF:

0.0190

Gnomad4 NFE

AF:

0.00963

Gnomad4 OTH

AF:

0.00333

Alfa

AF:

0.00729

Hom.:

Bravo

AF:

0.00519

ExAC

AF:

0.00187

AC:

Asia WGS

AF:

0.00203

AC:

AN:

3466

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

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2024

CABLES1: PP2, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.45

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.054

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.060

LIST_S2

Benign

0.67

MetaRNN

Benign

0.0035

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

MutationTaster

Benign

0.93

D;N

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.59

REVEL

Benign

0.068

Sift

Uncertain

0.010

Sift4G

Benign

0.76

Polyphen

0.30

Vest4

0.29

MPC

1.3

ClinPred

0.035

GERP RS

3.2

Varity_R

0.16

gMVP

0.54

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over