Genetic Variant NM_001100619.3:c.116C>G (chr18-23135878-C-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001100619.3(CABLES1):c.116C>G(p.Pro39Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000101 in 1,044,346 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00050 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000037 ( 0 hom. )

Consequence

CABLES1
NM_001100619.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.473

Publications

0 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 -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06064731).

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.116C>G	p.Pro39Arg	missense	Exon 1 of 10	NP_001094089.1	Q8TDN4-1
CABLES1	NM_001256438.1		c.-137+1208C>G		intron	N/A	NP_001243367.1	Q8TDN4-4
CABLES1	NR_023359.2		n.88+1227C>G		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CABLES1	ENST00000256925.12	TSL:1 MANE Select	c.116C>G	p.Pro39Arg	missense	Exon 1 of 10	ENSP00000256925.7	Q8TDN4-1
CABLES1	ENST00000877774.1		c.116C>G	p.Pro39Arg	missense	Exon 1 of 9	ENSP00000547833.1
CABLES1	ENST00000952329.1		c.116C>G	p.Pro39Arg	missense	Exon 1 of 9	ENSP00000622388.1

Frequencies

GnomAD3 genomes

AF:

0.000498

AC:

AN:

146684

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00174

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000135

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000368

AC:

AN:

897554

Hom.:

Cov.:

AF XY:

0.0000353

AC XY:

AN XY:

425006

show subpopulations

African (AFR)

AF:

0.00165

AC:

AN:

16950

American (AMR)

AF:

0.00

AC:

AN:

3484

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

6838

East Asian (EAS)

AF:

0.00

AC:

AN:

6530

South Asian (SAS)

AF:

0.00

AC:

AN:

19314

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5754

Middle Eastern (MID)

AF:

0.00103

AC:

AN:

1940

European-Non Finnish (NFE)

AF:

0.00000124

AC:

AN:

805996

Other (OTH)

AF:

0.0000650

AC:

AN:

30748

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

AF:

0.000497

AC:

AN:

146792

Hom.:

Cov.:

AF XY:

0.000434

AC XY:

AN XY:

71460

show subpopulations

African (AFR)

AF:

0.00173

AC:

AN:

40930

American (AMR)

AF:

0.000135

AC:

AN:

14782

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3390

East Asian (EAS)

AF:

0.00

AC:

AN:

5090

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

65932

Other (OTH)

AF:

0.00

AC:

AN:

2052

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000416

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

0.10

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.038

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.27

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.061

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.55

PhyloP100

0.47

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.030

REVEL

Benign

0.061

Sift

Uncertain

0.0060

Sift4G

Benign

0.13

Polyphen

0.057

Vest4

0.12

MutPred

0.19

Gain of helix (P = 0.005)

MVP

0.57

MPC

1.2

ClinPred

0.38

GERP RS

1.8

PromoterAI

-0.12

Neutral

(source)

Varity_R

0.065

gMVP

0.20

Mutation Taster

=92/8

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over