chr10-125019312-C-T

Variant names:

• chr10-125019312-C-T
• rs10901850
• NM_001329.4:c.59-15820G>A

Variant summary

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

The NM_001329.4(CTBP2):​c.59-15820G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 151,912 control chromosomes in the GnomAD database, including 11,329 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 0.38 (11329 hom., cov: 32)
• Consequence: CTBP2 NM_001329.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36
• Publications: 5 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=-1.04).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.434 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.59-15820G>A		intron	N/A	NP_001320.1	P56545-1
	CTBP2	NM_022802.3		c.1678+6770G>A		intron	N/A	NP_073713.2	P56545-2
	CTBP2	NM_001083914.3		c.59-15820G>A		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.59-15820G>A		intron	N/A	ENSP00000338615.5	P56545-1
	CTBP2	ENST00000309035.11	TSL:1	c.1678+6770G>A		intron	N/A	ENSP00000311825.6	P56545-2
	CTBP2	ENST00000411419.7	TSL:1	c.59-15820G>A		intron	N/A	ENSP00000410474.2	P56545-1

Frequencies

GnomAD3 genomes AF: 0.382 AC: 57951 AN: 151794 Hom.: 11320 Cov.: 32

Gnomad AFR AF: 0.436

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.385

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

GnomAD4 genome AF: 0.382 AC: 57995 AN: 151912 Hom.: 11329 Cov.: 32 AF XY: 0.378 AC XY: 28067 AN XY: 74220

African (AFR) AF: 0.435 AC: 18022 AN: 41396

American (AMR) AF: 0.443 AC: 6770 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.356 AC: 1235 AN: 3468

East Asian (EAS) AF: 0.269 AC: 1391 AN: 5172

South Asian (SAS) AF: 0.229 AC: 1102 AN: 4808

European-Finnish (FIN) AF: 0.327 AC: 3447 AN: 10532

Middle Eastern (MID) AF: 0.380 AC: 111 AN: 292

European-Non Finnish (NFE) AF: 0.365 AC: 24799 AN: 67950

Other (OTH) AF: 0.379 AC: 800 AN: 2112

Alfa AF: 0.374 Hom.: 35172

Bravo AF: 0.398

Asia WGS AF: 0.239 AC: 830 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.036
DANN	Benign	0.72
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10901850; hg19: chr10-126707881;