rs12769019

Variant names:

• chr10-125008758-A-G
• rs12769019
• NM_001329.4:c.59-5266T>C

Your query was ambiguous. Multiple possible variants found:

• chr10-125008758-A-G
• chr10-125008758-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001329.4(CTBP2):​c.59-5266T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 152,244 control chromosomes in the GnomAD database, including 4,411 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.23 (4411 hom., cov: 34)
• Consequence: CTBP2 NM_001329.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240
• Publications: 17 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001329.4. 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.59-5266T>C		intron	N/A	NP_001320.1	P56545-1
	CTBP2	NM_022802.3		c.1679-5266T>C		intron	N/A	NP_073713.2	P56545-2
	CTBP2	NM_001083914.3		c.59-5266T>C		intron	N/A	NP_001077383.1	P56545-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTBP2	ENST00000337195.11	TSL:1 MANE Select	c.59-5266T>C		intron	N/A	ENSP00000338615.5	P56545-1
	CTBP2	ENST00000309035.11	TSL:1	c.1679-5266T>C		intron	N/A	ENSP00000311825.6	P56545-2
	CTBP2	ENST00000411419.7	TSL:1	c.59-5266T>C		intron	N/A	ENSP00000410474.2	P56545-1

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34720 AN: 152126 Hom.: 4412 Cov.: 34

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.00981

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.255

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.228 AC: 34729 AN: 152244 Hom.: 4411 Cov.: 34 AF XY: 0.223 AC XY: 16609 AN XY: 74450

African (AFR) AF: 0.167 AC: 6925 AN: 41524

American (AMR) AF: 0.225 AC: 3435 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1070 AN: 3468

East Asian (EAS) AF: 0.00983 AC: 51 AN: 5188

South Asian (SAS) AF: 0.316 AC: 1528 AN: 4830

European-Finnish (FIN) AF: 0.149 AC: 1578 AN: 10602

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.282 AC: 19162 AN: 68016

Other (OTH) AF: 0.253 AC: 535 AN: 2114

Alfa AF: 0.126 Hom.: 224

Bravo AF: 0.229

Asia WGS AF: 0.127 AC: 443 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.7
DANN	Benign	0.56
PhyloP100		0.24
Mutation Taster		=100/0	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: rs12769019; hg19: chr10-126697327;