dbSNP rs1344128525: CTBP1:p.Ala409Ser (chr4-1212305-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001012614.2(CTBP1):c.1225G>T(p.Ala409Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 403,462 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A409T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000050 ( 0 hom. )

Consequence

CTBP1
NM_001012614.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.48

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.31632653).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012614.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CTBP1	NM_001012614.2	MANE Select	c.1225G>T	p.Ala409Ser	missense	Exon 10 of 10	NP_001012632.1	Q13363-2
CTBP1	NM_001377186.1		c.1261G>T	p.Ala421Ser	missense	Exon 9 of 9	NP_001364115.1
CTBP1	NM_001328.3		c.1258G>T	p.Ala420Ser	missense	Exon 9 of 9	NP_001319.1	X5D8Y5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CTBP1	ENST00000382952.8	TSL:1 MANE Select	c.1225G>T	p.Ala409Ser	missense	Exon 10 of 10	ENSP00000372411.3	Q13363-2
CTBP1	ENST00000290921.10	TSL:1	c.1258G>T	p.Ala420Ser	missense	Exon 9 of 9	ENSP00000290921.6	Q13363-1
CTBP1-AS	ENST00000625256.1	TSL:1	n.778C>A		non_coding_transcript_exon	Exon 3 of 6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000496

AC:

AN:

403462

Hom.:

Cov.:

AF XY:

0.00000934

AC XY:

AN XY:

214048

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

7280

American (AMR)

AF:

0.00

AC:

AN:

17242

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

8974

East Asian (EAS)

AF:

0.00

AC:

AN:

6882

South Asian (SAS)

AF:

0.00

AC:

AN:

54660

European-Finnish (FIN)

AF:

0.00

AC:

AN:

26982

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2358

European-Non Finnish (NFE)

AF:

0.00000760

AC:

AN:

263102

Other (OTH)

AF:

0.00

AC:

AN:

15982

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.0041

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.54

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.21

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.84

M_CAP

Pathogenic

0.49

MetaRNN

Benign

0.32

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.6

PhyloP100

3.5

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.44

REVEL

Uncertain

0.33

Sift

Benign

0.038

Sift4G

Benign

0.46

Polyphen

0.92

Vest4

0.37

MutPred

0.13

Gain of glycosylation at A420 (P = 0.0144)

MVP

0.60

MPC

0.66

ClinPred

0.71

GERP RS

3.9

Varity_R

0.14

gMVP

0.42

Mutation Taster

=83/17

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over