Variant 4-1212305-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001012614.2(CTBP1):c.1225G>A(p.Ala409Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000406 in 541,692 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000052 ( 0 hom. )

Consequence

CTBP1
NM_001012614.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.48

Variant links:

Genes affected

CTBP1 (HGNC:2494): (C-terminal binding protein 1) This gene encodes a protein that binds to the C-terminus of adenovirus E1A proteins. This phosphoprotein is a transcriptional repressor and may play a role during cellular proliferation. This protein and the product of a second closely related gene, CTBP2, can dimerize. Both proteins can also interact with a polycomb group protein complex which participates in regulation of gene expression during development. Alternative splicing of transcripts from this gene results in multiple transcript variants. [provided by RefSeq, Jul 2008]

CTBP1 links:

CTBP1-AS (HGNC:48337): (CTBP1 antisense RNA)

CTBP1-AS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.23609981).

BS2

High AC in GnomAdExome4 at 21 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTBP1	NM_001012614.2 link	c.1225G>A	p.Ala409Thr	missense_variant	10/10	ENST00000382952.8	NP_001012632.1	Q13363-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTBP1	ENST00000382952.8 link	c.1225G>A	p.Ala409Thr	missense_variant	10/10	1	NM_001012614.2	ENSP00000372411.3		Q13363-2

Frequencies

GnomAD3 genomes

AF:

0.00000723

AC:

AN:

138230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000259

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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

GnomAD3 exomes

AF:

0.0000152

AC:

AN:

131682

Hom.:

AF XY:

0.00

AC XY:

AN XY:

73534

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000133

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000659

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000520

AC:

AN:

403462

Hom.:

Cov.:

AF XY:

0.0000467

AC XY:

AN XY:

214048

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000366

Gnomad4 FIN exome

AF:

0.0000371

Gnomad4 NFE exome

AF:

0.0000684

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000723

AC:

AN:

138230

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

66840

show subpopulations

Gnomad4 AFR

AF:

0.0000259

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000291

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Hypotonia, ataxia, developmental delay, and tooth enamel defect syndrome

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center

Dec 19, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.021

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.34

.;T

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.31

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.94

D;D

M_CAP

Pathogenic

0.47

MetaRNN

Benign

0.24

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.82

.;L

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.68

N;N

REVEL

Uncertain

0.36

Sift

Benign

0.24

T;T

Sift4G

Benign

0.48

T;T

Polyphen

0.14

.;B

Vest4

0.23

MutPred

0.11

.;Gain of glycosylation at A420 (P = 9e-04);

MVP

0.62

MPC

0.46

ClinPred

0.36

GERP RS

3.9

Varity_R

0.11

gMVP

0.52

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