Variant rs3781409 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The ENST00000309035.11(CTBP2):c.700G>A(p.Val234Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 1,613,106 control chromosomes in the GnomAD database, including 53,878 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.22 ( 3951 hom., cov: 33)

Exomes 𝑓: 0.26 ( 49927 hom. )

Consequence

CTBP2
ENST00000309035.11 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.06

Variant links:

Genes affected

CTBP2 (HGNC:2495): (C-terminal binding protein 2) This gene produces alternative transcripts encoding two distinct proteins. One protein is a transcriptional repressor, while the other isoform is a major component of specialized synapses known as synaptic ribbons. Both proteins contain a NAD+ binding domain similar to NAD+-dependent 2-hydroxyacid dehydrogenases. A portion of the 3' untranslated region was used to map this gene to chromosome 21q21.3; however, it was noted that similar loci elsewhere in the genome are likely. Blast analysis shows that this gene is present on chromosome 10. Several transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Feb 2014]

CTBP2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001383245).

BP6

Variant 10-125027060-C-T is Benign according to our data. Variant chr10-125027060-C-T is described in ClinVar as [Benign]. Clinvar id is 3059060.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTBP2	NM_022802.3 linkuse as main transcript	c.700G>A	p.Val234Met	missense_variant	1/9	ENST00000309035.11	NP_073713.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTBP2	ENST00000309035.11 linkuse as main transcript	c.700G>A	p.Val234Met	missense_variant	1/9	1	NM_022802.3	ENSP00000311825		P56545-2

Frequencies

GnomAD3 genomes

AF:

0.216

AC:

32917

AN:

152114

Hom.:

3951

Cov.:

show subpopulations

Gnomad AFR

AF:

0.121

Gnomad AMI

AF:

0.389

Gnomad AMR

AF:

0.248

Gnomad ASJ

AF:

0.246

Gnomad EAS

AF:

0.277

Gnomad SAS

AF:

0.183

Gnomad FIN

AF:

0.193

Gnomad MID

AF:

0.256

Gnomad NFE

AF:

0.264

Gnomad OTH

AF:

0.229

GnomAD3 exomes

AF:

0.240

AC:

59750

AN:

249338

Hom.:

7478

AF XY:

0.238

AC XY:

32126

AN XY:

135242

show subpopulations

Gnomad AFR exome

AF:

0.120

Gnomad AMR exome

AF:

0.266

Gnomad ASJ exome

AF:

0.243

Gnomad EAS exome

AF:

0.266

Gnomad SAS exome

AF:

0.180

Gnomad FIN exome

AF:

0.201

Gnomad NFE exome

AF:

0.267

Gnomad OTH exome

AF:

0.255

GnomAD4 exome

AF:

0.259

AC:

378277

AN:

1460874

Hom.:

49927

Cov.:

AF XY:

0.257

AC XY:

186631

AN XY:

726638

show subpopulations

Gnomad4 AFR exome

AF:

0.114

Gnomad4 AMR exome

AF:

0.264

Gnomad4 ASJ exome

AF:

0.246

Gnomad4 EAS exome

AF:

0.297

Gnomad4 SAS exome

AF:

0.183

Gnomad4 FIN exome

AF:

0.204

Gnomad4 NFE exome

AF:

0.271

Gnomad4 OTH exome

AF:

0.247

GnomAD4 genome

AF:

0.216

AC:

32924

AN:

152232

Hom.:

3951

Cov.:

AF XY:

0.214

AC XY:

15917

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.121

Gnomad4 AMR

AF:

0.248

Gnomad4 ASJ

AF:

0.246

Gnomad4 EAS

AF:

0.277

Gnomad4 SAS

AF:

0.183

Gnomad4 FIN

AF:

0.193

Gnomad4 NFE

AF:

0.264

Gnomad4 OTH

AF:

0.226

Alfa

AF:

0.260

Hom.:

8072

Bravo

AF:

0.220

TwinsUK

AF:

0.279

AC:

1034

ALSPAC

AF:

0.285

AC:

1099

ESP6500AA

AF:

0.123

AC:

541

ESP6500EA

AF:

0.265

AC:

2280

ExAC

AF:

0.237

AC:

28836

Asia WGS

AF:

0.184

AC:

639

AN:

3478

EpiCase

AF:

0.267

EpiControl

AF:

0.272

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CTBP2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 28, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Pathogenic

1.0

Eigen

Benign

-0.014

Eigen_PC

Benign

0.081

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.74

MetaRNN

Benign

0.0014

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.025

P;P;P;P;P

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.80

REVEL

Benign

0.21

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0080

Polyphen

0.21

Vest4

0.10

MPC

0.52

ClinPred

0.030

GERP RS

3.6

gMVP

0.22

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