rs3781409

Variant names:

• chr10-125027060-C-T
• rs3781409
• ENST00000309035.11:c.700G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-125027060-C-T
• chr10-125027060-C-A
• chr10-125027060-C-G

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.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. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.22 (3951 hom., cov: 33)
  • Exomes 𝑓: 0.26 (49927 hom.)
• Consequence: CTBP2 NM_022802.3 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 3.06
• Publications: 19 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=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 VariationId 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.

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+11937G>A		intron	N/A	NP_001320.1	P56545-1
	CTBP2	NM_022802.3		c.700G>A	p.Val234Met	missense	Exon 1 of 9	NP_073713.2	P56545-2
	CTBP2	NM_001083914.3		c.58+11937G>A		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.700G>A	p.Val234Met	missense	Exon 1 of 9	ENSP00000311825.6	P56545-2
	CTBP2	ENST00000337195.11	TSL:1 MANE Select	c.58+11937G>A		intron	N/A	ENSP00000338615.5	P56545-1
	CTBP2	ENST00000411419.7	TSL:1	c.58+11937G>A		intron	N/A	ENSP00000410474.2	P56545-1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32917 AN: 152114 Hom.: 3951 Cov.: 33

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

GnomAD2 exomes AF: 0.240 AC: 59750 AN: 249338 AF XY: 0.238

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 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.: 94 AF XY: 0.257 AC XY: 186631 AN XY: 726638

African (AFR) AF: 0.114 AC: 3818 AN: 33466

American (AMR) AF: 0.264 AC: 11805 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 6415 AN: 26110

East Asian (EAS) AF: 0.297 AC: 11793 AN: 39682

South Asian (SAS) AF: 0.183 AC: 15743 AN: 86232

European-Finnish (FIN) AF: 0.204 AC: 10796 AN: 53042

Middle Eastern (MID) AF: 0.231 AC: 1331 AN: 5768

European-Non Finnish (NFE) AF: 0.271 AC: 301680 AN: 1111520

Other (OTH) AF: 0.247 AC: 14896 AN: 60372

GnomAD4 genome AF: 0.216 AC: 32924 AN: 152232 Hom.: 3951 Cov.: 33 AF XY: 0.214 AC XY: 15917 AN XY: 74446

African (AFR) AF: 0.121 AC: 5036 AN: 41542

American (AMR) AF: 0.248 AC: 3791 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 853 AN: 3470

East Asian (EAS) AF: 0.277 AC: 1432 AN: 5164

South Asian (SAS) AF: 0.183 AC: 882 AN: 4832

European-Finnish (FIN) AF: 0.193 AC: 2052 AN: 10616

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.264 AC: 17965 AN: 67978

Other (OTH) AF: 0.226 AC: 478 AN: 2116

Alfa AF: 0.257 Hom.: 18513

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

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	0.14
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	21
DANN	Pathogenic	1.0
Eigen	Benign	-0.014
Eigen_PC	Benign	0.081
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.74	T
MetaRNN	Benign	0.0014	T
MetaSVM	Benign	-1.1	T
PhyloP100		3.1
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.80	N
REVEL	Benign	0.21
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0080	D
Polyphen		0.21	B
Vest4		0.10
MPC		0.52
ClinPred		0.030	T
GERP RS		3.6
gMVP		0.22
Mutation Taster		=73/27	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: rs3781409; hg19: chr10-126715629; COSMIC: COSV58339247;