chr4-1248917-A-C

Position:

chr4-1248917-A-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001012614.2(CTBP1):c.-190T>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000015 in 132,958 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 (★).

Frequency

Genomes: 𝑓 0.000015 ( 0 hom., cov: 29)

Exomes 𝑓: 0.0000024 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CTBP1
NM_001012614.2 5_prime_UTR_premature_start_codon_gain

Scores

Splicing: ADA: 0.00004239

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -5.39

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 (HGNC:):

CTBP1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
CTBP1	NM_001012614.2 linkuse as main transcript	c.-190T>G	5_prime_UTR_premature_start_codon_gain_variant	1/10	ENST00000382952.8	NP_001012632.1	Q13363-2
CTBP1	NM_001012614.2 linkuse as main transcript	c.-190T>G	splice_region_variant	1/10	ENST00000382952.8	NP_001012632.1	Q13363-2
CTBP1	NM_001012614.2 linkuse as main transcript	c.-190T>G	5_prime_UTR_variant	1/10	ENST00000382952.8	NP_001012632.1	Q13363-2

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CTBP1	ENST00000382952.8 linkuse as main transcript	c.-190T>G	5_prime_UTR_premature_start_codon_gain_variant	1/10	1	NM_001012614.2	ENSP00000372411.3	Q13363-2
CTBP1	ENST00000382952.8 linkuse as main transcript	c.-190T>G	splice_region_variant	1/10	1	NM_001012614.2	ENSP00000372411.3	Q13363-2
CTBP1	ENST00000382952.8 linkuse as main transcript	c.-190T>G	5_prime_UTR_variant	1/10	1	NM_001012614.2	ENSP00000372411.3	Q13363-2

Frequencies

GnomAD3 genomes

AF:

0.0000150

AC:

AN:

132958

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000271

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:

0.0000162

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000235

AC:

AN:

849522

Hom.:

Cov.:

AF XY:

0.00000252

AC XY:

AN XY:

396510

show subpopulations

Gnomad4 AFR exome

AF:

0.0000630

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000130

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000150

AC:

AN:

132958

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

64164

show subpopulations

Gnomad4 AFR

AF:

0.0000271

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:

0.0000162

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 14, 2023

This variant has not been reported in the literature in individuals affected with CTBP1-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the gnomAD database. This sequence change affects codon 13 of the CTBP1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the CTBP1 protein. It affects a nucleotide within the consensus splice site. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

9.0

DANN

Benign

0.90

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000042

dbscSNV1_RF

Benign

0.072

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