ENST00000309035.11:c.1615C>G

Variant names:

• chr10-125026145-G-C
• rs2946994
• ENST00000309035.11:c.1615C>G

Variant summary

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

The ENST00000309035.11(CTBP2):​c.1615C>G​(p.Gln539Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.483 in 1,605,108 control chromosomes in the GnomAD database, including 189,647 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.46 (16663 hom., cov: 33)
  • Exomes 𝑓: 0.49 (172984 hom.)
• Consequence: CTBP2 ENST00000309035.11 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 9.86
• 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=1.8411875E-4).
• BP6: Variant 10-125026145-G-C is Benign according to our data. Variant chr10-125026145-G-C is described in ClinVar as Benign. ClinVar VariationId is 3059384.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.61 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000309035.11. 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+12852C>G		intron	N/A	NP_001320.1	P56545-1
	CTBP2	NM_022802.3		c.1615C>G	p.Gln539Glu	missense	Exon 1 of 9	NP_073713.2	P56545-2
	CTBP2	NM_001083914.3		c.58+12852C>G		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.1615C>G	p.Gln539Glu	missense	Exon 1 of 9	ENSP00000311825.6	P56545-2
	CTBP2	ENST00000337195.11	TSL:1 MANE Select	c.58+12852C>G		intron	N/A	ENSP00000338615.5	P56545-1
	CTBP2	ENST00000411419.7	TSL:1	c.58+12852C>G		intron	N/A	ENSP00000410474.2	P56545-1

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70181 AN: 152010 Hom.: 16652 Cov.: 33

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.446

GnomAD2 exomes AF: 0.475 AC: 117146 AN: 246448 AF XY: 0.480

Gnomad AFR exome AF: 0.375

Gnomad AMR exome AF: 0.334

Gnomad ASJ exome AF: 0.476

Gnomad EAS exome AF: 0.648

Gnomad FIN exome AF: 0.562

Gnomad NFE exome AF: 0.495

Gnomad OTH exome AF: 0.471

GnomAD4 exome AF: 0.485 AC: 704806 AN: 1452980 Hom.: 172984 Cov.: 72 AF XY: 0.485 AC XY: 349765 AN XY: 721088

African (AFR) AF: 0.385 AC: 12812 AN: 33290

American (AMR) AF: 0.335 AC: 14899 AN: 44420

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 12180 AN: 25762

East Asian (EAS) AF: 0.585 AC: 23093 AN: 39448

South Asian (SAS) AF: 0.448 AC: 38407 AN: 85760

European-Finnish (FIN) AF: 0.558 AC: 29600 AN: 53084

Middle Eastern (MID) AF: 0.444 AC: 2539 AN: 5724

European-Non Finnish (NFE) AF: 0.490 AC: 542264 AN: 1105540

Other (OTH) AF: 0.484 AC: 29012 AN: 59952

GnomAD4 genome AF: 0.462 AC: 70229 AN: 152128 Hom.: 16663 Cov.: 33 AF XY: 0.465 AC XY: 34548 AN XY: 74370

African (AFR) AF: 0.386 AC: 16037 AN: 41496

American (AMR) AF: 0.372 AC: 5688 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 1652 AN: 3472

East Asian (EAS) AF: 0.628 AC: 3236 AN: 5152

South Asian (SAS) AF: 0.467 AC: 2257 AN: 4828

European-Finnish (FIN) AF: 0.580 AC: 6142 AN: 10598

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.496 AC: 33730 AN: 67970

Other (OTH) AF: 0.450 AC: 951 AN: 2114

Alfa AF: 0.474 Hom.: 12825

Bravo AF: 0.441

TwinsUK AF: 0.486 AC: 1801

ALSPAC AF: 0.479 AC: 1847

ESP6500AA AF: 0.385 AC: 1695

ESP6500EA AF: 0.496 AC: 4263

ExAC AF: 0.479 AC: 58112

Asia WGS AF: 0.560 AC: 1952 AN: 3478

EpiCase AF: 0.490

EpiControl AF: 0.482

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	0.13
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	24
DANN	Uncertain	0.99
Eigen	Uncertain	0.64
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.56	T
MetaRNN	Benign	0.00018	T
MetaSVM	Benign	-0.90	T
PhyloP100		9.9
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.37	N
REVEL	Uncertain	0.35
Sift	Benign	0.086	T
Sift4G	Benign	0.23	T
Polyphen		0.93	P
Vest4		0.12
MPC		0.12
ClinPred		0.040	T
GERP RS		5.3
gMVP		0.23
Mutation Taster		=71/29	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: rs2946994; hg19: chr10-126714714; COSMIC: COSV58339122;