rs41303611

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6BS1BS2

The NM_001363508.2(CTBP2):c.208G>A(p.Gly70Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0197 in 1,612,740 control chromosomes in the GnomAD database, including 392 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.014 ( 25 hom., cov: 32)

Exomes 𝑓: 0.020 ( 367 hom. )

Consequence

CTBP2
NM_001363508.2 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -2.57

Publications

5 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP6

Variant 10-125005601-C-T is Benign according to our data. Variant chr10-125005601-C-T is described in ClinVar as Benign. ClinVar VariationId is 3042376.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0137 (2090/152358) while in subpopulation NFE AF = 0.0221 (1502/68024). AF 95% confidence interval is 0.0212. There are 25 homozygotes in GnomAd4. There are 1015 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 2090 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363508.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CTBP2	NM_001329.4	MANE Select	c.59-2109G>A		intron	N/A	NP_001320.1	P56545-1
CTBP2	NM_001363508.2		c.208G>A	p.Gly70Arg	missense	Exon 1 of 9	NP_001350437.1	P56545-3
CTBP2	NM_022802.3		c.1679-2109G>A		intron	N/A	NP_073713.2	P56545-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CTBP2	ENST00000334808.10	TSL:1	c.208G>A	p.Gly70Arg	missense	Exon 1 of 9	ENSP00000357816.5	P56545-3
CTBP2	ENST00000337195.11	TSL:1 MANE Select	c.59-2109G>A		intron	N/A	ENSP00000338615.5	P56545-1
CTBP2	ENST00000309035.11	TSL:1	c.1679-2109G>A		intron	N/A	ENSP00000311825.6	P56545-2

Frequencies

GnomAD3 genomes

AF:

0.0137

AC:

2091

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00326

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00942

Gnomad ASJ

AF:

0.0320

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0143

Gnomad FIN

AF:

0.00809

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0221

Gnomad OTH

AF:

0.0196

GnomAD2 exomes

AF:

0.0157

AC:

3792

AN:

241022

AF XY:

0.0166

show subpopulations

Gnomad AFR exome

AF:

0.00337

Gnomad AMR exome

AF:

0.00716

Gnomad ASJ exome

AF:

0.0259

Gnomad EAS exome

AF:

0.0000560

Gnomad FIN exome

AF:

0.00850

Gnomad NFE exome

AF:

0.0231

Gnomad OTH exome

AF:

0.0194

GnomAD4 exome

AF:

0.0203

AC:

29624

AN:

1460382

Hom.:

367

Cov.:

AF XY:

0.0203

AC XY:

14743

AN XY:

726460

show subpopulations

African (AFR)

AF:

0.00305

AC:

102

AN:

33476

American (AMR)

AF:

0.00808

AC:

361

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.0256

AC:

669

AN:

26134

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39694

South Asian (SAS)

AF:

0.0158

AC:

1365

AN:

86244

European-Finnish (FIN)

AF:

0.00984

AC:

514

AN:

52242

Middle Eastern (MID)

AF:

0.0210

AC:

121

AN:

5768

European-Non Finnish (NFE)

AF:

0.0229

AC:

25413

AN:

1111768

Other (OTH)

AF:

0.0178

AC:

1076

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

1815

3629

5444

7258

9073

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

910

1820

2730

3640

4550

<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:

0.0137

AC:

2090

AN:

152358

Hom.:

Cov.:

AF XY:

0.0136

AC XY:

1015

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.00325

AC:

135

AN:

41580

American (AMR)

AF:

0.00934

AC:

143

AN:

15314

Ashkenazi Jewish (ASJ)

AF:

0.0320

AC:

111

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5186

South Asian (SAS)

AF:

0.0143

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00809

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0221

AC:

1502

AN:

68024

Other (OTH)

AF:

0.0194

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

114

228

343

457

571

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

150

<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:

0.0165

Hom.:

Bravo

AF:

0.0133

ESP6500AA

AF:

0.00285

AC:

ESP6500EA

AF:

0.0224

AC:

ExAC

AF:

0.0159

AC:

1877

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.0236

EpiControl

AF:

0.0209

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

CTBP2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.40

CADD

Benign

4.9

(source)

DANN

Benign

0.84

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.42

MetaRNN

Benign

0.0037

MetaSVM

Benign

-0.77

PhyloP100

-2.6

PROVEAN

Benign

-0.62

REVEL

Benign

0.19

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0060

Vest4

0.030

MutPred

0.54

Gain of solvent accessibility (P = 6e-04)

ClinPred

0.0062

GERP RS

-1.2

PromoterAI

0.076

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.23

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.23

Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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