Genetic Variant CABLES1:p.Ala114Val (chr18-23136103-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001100619.3(CABLES1):c.341C>T(p.Ala114Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000212 in 1,035,570 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000021 ( 1 hom. )

Consequence

CABLES1
NM_001100619.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.08

Publications

1 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.15245202).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001100619.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CABLES1	NM_001100619.3	MANE Select	c.341C>T	p.Ala114Val	missense	Exon 1 of 10	NP_001094089.1	Q8TDN4-1
CABLES1	NM_001256438.1		c.-137+1433C>T		intron	N/A	NP_001243367.1	Q8TDN4-4
CABLES1	NR_023359.2		n.88+1452C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CABLES1	ENST00000256925.12	TSL:1 MANE Select	c.341C>T	p.Ala114Val	missense	Exon 1 of 10	ENSP00000256925.7	Q8TDN4-1
CABLES1	ENST00000877774.1		c.341C>T	p.Ala114Val	missense	Exon 1 of 9	ENSP00000547833.1
CABLES1	ENST00000952329.1		c.341C>T	p.Ala114Val	missense	Exon 1 of 9	ENSP00000622388.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

1104

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000212

AC:

AN:

1035570

Hom.:

Cov.:

AF XY:

0.0000163

AC XY:

AN XY:

489646

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

21064

American (AMR)

AF:

0.00

AC:

AN:

6780

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12000

East Asian (EAS)

AF:

0.0000454

AC:

AN:

22014

South Asian (SAS)

AF:

0.000712

AC:

AN:

19662

European-Finnish (FIN)

AF:

0.00

AC:

AN:

19588

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2682

European-Non Finnish (NFE)

AF:

0.00000673

AC:

AN:

891808

Other (OTH)

AF:

0.0000250

AC:

AN:

39972

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.056

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.50

M_CAP

Benign

0.071

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.55

PhyloP100

3.1

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.89

REVEL

Benign

0.052

Sift

Pathogenic

0.0

Sift4G

Benign

0.16

Polyphen

0.75

Vest4

0.087

MutPred

0.32

Gain of MoRF binding (P = 0.1078)

MVP

0.41

MPC

1.1

ClinPred

0.44

GERP RS

1.6

PromoterAI

-0.099

Neutral

(source)

Varity_R

0.21

gMVP

0.25

Mutation Taster

=87/13

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over