10-125026072-G-C

Variant names:

• chr10-125026072-G-C
• rs12571821
• NM_001329.4:c.58+12925C>G

Variant summary

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

The NM_001329.4(CTBP2):​c.58+12925C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0318 in 1,548,982 control chromosomes in the GnomAD database, including 987 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.025 (67 hom., cov: 33)
  • Exomes 𝑓: 0.033 (920 hom.)
• Consequence: CTBP2 NM_001329.4 intron
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.61
• 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 10-125026072-G-C is Benign according to our data. Variant chr10-125026072-G-C is described in ClinVar as Benign. ClinVar VariationId is 3060493.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0563 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.58+12925C>G		intron	N/A	NP_001320.1	P56545-1
	CTBP2	NM_022802.3		c.1678+10C>G		intron	N/A	NP_073713.2	P56545-2
	CTBP2	NM_001083914.3		c.58+12925C>G		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.58+12925C>G		intron	N/A	ENSP00000338615.5	P56545-1
	CTBP2	ENST00000309035.11	TSL:1	c.1678+10C>G		intron	N/A	ENSP00000311825.6	P56545-2
	CTBP2	ENST00000411419.7	TSL:1	c.58+12925C>G		intron	N/A	ENSP00000410474.2	P56545-1

Frequencies

GnomAD3 genomes AF: 0.0248 AC: 3780 AN: 152188 Hom.: 63 Cov.: 33

Gnomad AFR AF: 0.00572

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0374

Gnomad ASJ AF: 0.0452

Gnomad EAS AF: 0.0392

Gnomad SAS AF: 0.0549

Gnomad FIN AF: 0.0166

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0307

Gnomad OTH AF: 0.0344

GnomAD2 exomes AF: 0.0331 AC: 6811 AN: 205470 AF XY: 0.0341

Gnomad AFR exome AF: 0.00568

Gnomad AMR exome AF: 0.0423

Gnomad ASJ exome AF: 0.0360

Gnomad EAS exome AF: 0.0294

Gnomad FIN exome AF: 0.0200

Gnomad NFE exome AF: 0.0331

Gnomad OTH exome AF: 0.0374

GnomAD4 exome AF: 0.0325 AC: 45441 AN: 1396676 Hom.: 920 Cov.: 31 AF XY: 0.0333 AC XY: 22802 AN XY: 685010

African (AFR) AF: 0.00485 AC: 156 AN: 32168

American (AMR) AF: 0.0435 AC: 1727 AN: 39722

Ashkenazi Jewish (ASJ) AF: 0.0364 AC: 801 AN: 21996

East Asian (EAS) AF: 0.0583 AC: 2271 AN: 38940

South Asian (SAS) AF: 0.0543 AC: 4140 AN: 76186

European-Finnish (FIN) AF: 0.0226 AC: 1143 AN: 50542

Middle Eastern (MID) AF: 0.0570 AC: 309 AN: 5418

European-Non Finnish (NFE) AF: 0.0306 AC: 32834 AN: 1074258

Other (OTH) AF: 0.0359 AC: 2060 AN: 57446

GnomAD4 genome AF: 0.0249 AC: 3794 AN: 152306 Hom.: 67 Cov.: 33 AF XY: 0.0255 AC XY: 1900 AN XY: 74478

African (AFR) AF: 0.00573 AC: 238 AN: 41572

American (AMR) AF: 0.0372 AC: 569 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0452 AC: 157 AN: 3472

East Asian (EAS) AF: 0.0393 AC: 203 AN: 5166

South Asian (SAS) AF: 0.0550 AC: 265 AN: 4820

European-Finnish (FIN) AF: 0.0166 AC: 176 AN: 10626

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0307 AC: 2087 AN: 68026

Other (OTH) AF: 0.0406 AC: 86 AN: 2116

Alfa AF: 0.0181 Hom.: 21

Bravo AF: 0.0237

Asia WGS AF: 0.0810 AC: 283 AN: 3478

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
BayesDel_noAF	Benign	-0.76
CADD	Benign	12
DANN	Benign	0.71
PhyloP100		1.6
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: rs12571821; hg19: chr10-126714641;