rs28477404

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001100619.3(CABLES1):c.341C>A(p.Ala114Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000986 in 1,185,776 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A114V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0051 ( 4 hom., cov: 33)

Exomes 𝑓: 0.00039 ( 4 hom. )

Consequence

CABLES1
NM_001100619.3 missense

Scores

Clinical Significance

Not reported in ClinVar

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017751753).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00513 (770/150204) while in subpopulation AFR AF = 0.0177 (731/41310). AF 95% confidence interval is 0.0166. There are 4 homozygotes in GnomAd4. There are 355 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 4 gene

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>A	p.Ala114Asp	missense	Exon 1 of 10	NP_001094089.1	Q8TDN4-1
CABLES1	NM_001256438.1		c.-137+1433C>A		intron	N/A	NP_001243367.1	Q8TDN4-4
CABLES1	NR_023359.2		n.88+1452C>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CABLES1	ENST00000256925.12	TSL:1 MANE Select	c.341C>A	p.Ala114Asp	missense	Exon 1 of 10	ENSP00000256925.7	Q8TDN4-1
CABLES1	ENST00000877774.1		c.341C>A	p.Ala114Asp	missense	Exon 1 of 9	ENSP00000547833.1
CABLES1	ENST00000952329.1		c.341C>A	p.Ala114Asp	missense	Exon 1 of 9	ENSP00000622388.1

Frequencies

GnomAD3 genomes

AF:

0.00513

AC:

770

AN:

150096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0177

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00159

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:

0.000119

Gnomad OTH

AF:

0.00339

GnomAD2 exomes

AF:

0.00181

AC:

AN:

1104

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.0526

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:

0.000385

AC:

399

AN:

1035572

Hom.:

Cov.:

AF XY:

0.000355

AC XY:

174

AN XY:

489646

show subpopulations

African (AFR)

AF:

0.0167

AC:

351

AN:

21064

American (AMR)

AF:

0.00103

AC:

AN:

6780

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12000

East Asian (EAS)

AF:

0.00

AC:

AN:

22014

South Asian (SAS)

AF:

0.00

AC:

AN:

19662

European-Finnish (FIN)

AF:

0.00

AC:

AN:

19590

Middle Eastern (MID)

AF:

0.000746

AC:

AN:

2682

European-Non Finnish (NFE)

AF:

0.0000146

AC:

AN:

891808

Other (OTH)

AF:

0.000650

AC:

AN:

39972

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

104

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00513

AC:

770

AN:

150204

Hom.:

Cov.:

AF XY:

0.00484

AC XY:

355

AN XY:

73330

show subpopulations

African (AFR)

AF:

0.0177

AC:

731

AN:

41310

American (AMR)

AF:

0.00159

AC:

AN:

15102

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3452

East Asian (EAS)

AF:

0.00

AC:

AN:

5114

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9832

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.000119

AC:

AN:

67282

Other (OTH)

AF:

0.00336

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

126

168

210

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:

0.00444

Hom.:

ExAC

AF:

0.000626

AC:

Asia WGS

AF:

0.000641

AC:

AN:

3134

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.053

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.39

MetaRNN

Benign

0.0018

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.55

PhyloP100

3.1

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

0.13

REVEL

Benign

0.086

Sift

Pathogenic

0.0

Sift4G

Benign

0.083

Polyphen

0.91

Vest4

0.22

MVP

0.51

MPC

1.6

ClinPred

0.13

GERP RS

1.6

PromoterAI

-0.0069

Neutral

(source)

Varity_R

0.37

gMVP

0.22

Mutation Taster

=77/23

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