rs3012075

Variant names:

• chr10-125026397-A-G
• rs3012075
• ENST00000309035.11:c.1363T>C

Your query was ambiguous. Multiple possible variants found:

• chr10-125026397-A-G
• chr10-125026397-A-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_022802.3(CTBP2):​c.1363T>C​(p.Tyr455His) variant causes a missense change. The variant allele was found at a frequency of 0.481 in 1,609,638 control chromosomes in the GnomAD database, including 189,586 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.45 (15791 hom., cov: 32)
  • Exomes 𝑓: 0.48 (173795 hom.)
• Consequence: CTBP2 NM_022802.3 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 3.95
• Publications: 23 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.5206962E-5).
• BP6: Variant 10-125026397-A-G is Benign according to our data. Variant chr10-125026397-A-G is described in ClinVar as Benign. ClinVar VariationId is 3059822.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022802.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTBP2	NM_001329.4	MANE Select	c.58+12600T>C		intron	N/A	NP_001320.1	P56545-1
	CTBP2	NM_022802.3		c.1363T>C	p.Tyr455His	missense	Exon 1 of 9	NP_073713.2	P56545-2
	CTBP2	NM_001083914.3		c.58+12600T>C		intron	N/A	NP_001077383.1	P56545-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTBP2	ENST00000309035.11	TSL:1	c.1363T>C	p.Tyr455His	missense	Exon 1 of 9	ENSP00000311825.6	P56545-2
	CTBP2	ENST00000337195.11	TSL:1 MANE Select	c.58+12600T>C		intron	N/A	ENSP00000338615.5	P56545-1
	CTBP2	ENST00000411419.7	TSL:1	c.58+12600T>C		intron	N/A	ENSP00000410474.2	P56545-1

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67639 AN: 151694 Hom.: 15788 Cov.: 32

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.628

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.435

GnomAD2 exomes AF: 0.472 AC: 115693 AN: 244920 AF XY: 0.478

Gnomad AFR exome AF: 0.315

Gnomad AMR exome AF: 0.332

Gnomad ASJ exome AF: 0.476

Gnomad EAS exome AF: 0.648

Gnomad FIN exome AF: 0.569

Gnomad NFE exome AF: 0.497

Gnomad OTH exome AF: 0.469

GnomAD4 exome AF: 0.485 AC: 706848 AN: 1457826 Hom.: 173795 Cov.: 68 AF XY: 0.485 AC XY: 351357 AN XY: 724408

African (AFR) AF: 0.323 AC: 10802 AN: 33394

American (AMR) AF: 0.334 AC: 14881 AN: 44606

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 12302 AN: 26018

East Asian (EAS) AF: 0.585 AC: 23163 AN: 39564

South Asian (SAS) AF: 0.447 AC: 38492 AN: 86164

European-Finnish (FIN) AF: 0.564 AC: 29960 AN: 53136

Middle Eastern (MID) AF: 0.442 AC: 2539 AN: 5748

European-Non Finnish (NFE) AF: 0.492 AC: 545752 AN: 1109020

Other (OTH) AF: 0.481 AC: 28957 AN: 60176

GnomAD4 genome AF: 0.446 AC: 67677 AN: 151812 Hom.: 15791 Cov.: 32 AF XY: 0.449 AC XY: 33284 AN XY: 74200

African (AFR) AF: 0.328 AC: 13598 AN: 41428

American (AMR) AF: 0.366 AC: 5593 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 1651 AN: 3470

East Asian (EAS) AF: 0.627 AC: 3192 AN: 5088

South Asian (SAS) AF: 0.465 AC: 2231 AN: 4800

European-Finnish (FIN) AF: 0.586 AC: 6195 AN: 10580

Middle Eastern (MID) AF: 0.425 AC: 124 AN: 292

European-Non Finnish (NFE) AF: 0.497 AC: 33753 AN: 67850

Other (OTH) AF: 0.439 AC: 926 AN: 2110

Alfa AF: 0.481 Hom.: 37046

Bravo AF: 0.423

TwinsUK AF: 0.486 AC: 1801

ALSPAC AF: 0.482 AC: 1859

ESP6500AA AF: 0.329 AC: 1449

ESP6500EA AF: 0.497 AC: 4276

ExAC AF: 0.474 AC: 57527

Asia WGS AF: 0.555 AC: 1932 AN: 3478

EpiCase AF: 0.492

EpiControl AF: 0.484

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	CTBP2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	17
DANN	Uncertain	1.0
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.38	T
MetaRNN	Benign	0.000025	T
MetaSVM	Benign	-0.94	T
PhyloP100		3.9
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.51	N
REVEL	Benign	0.21
Sift	Benign	0.031	D
Sift4G	Benign	0.18	T
Polyphen		0.0010	B
Vest4		0.11
MPC		0.13
ClinPred		0.024	T
GERP RS		4.0
gMVP		0.36
Mutation Taster		=91/9	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3012075; hg19: chr10-126714966; COSMIC: COSV58338964;