chr10-125087919-A-G

Variant names:

• chr10-125087919-A-G
• rs1152659
• NM_001329.4:c.-102+23071T>C

Variant summary

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

The NM_001329.4(CTBP2):​c.-102+23071T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 152,130 control chromosomes in the GnomAD database, including 7,030 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 0.29 (7030 hom., cov: 32)
• Consequence: CTBP2 NM_001329.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31
• Publications: 2 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.367 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTBP2	NM_001329.4	MANE Select	c.-102+23071T>C		intron	N/A	NP_001320.1
	CTBP2	NM_001083914.3		c.-102+23071T>C		intron	N/A	NP_001077383.1
	CTBP2	NM_001290214.3		c.-102+45593T>C		intron	N/A	NP_001277143.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTBP2	ENST00000337195.11	TSL:1 MANE Select	c.-102+23071T>C		intron	N/A	ENSP00000338615.5
	CTBP2	ENST00000411419.7	TSL:1	c.-102+23071T>C		intron	N/A	ENSP00000410474.2
	CTBP2	ENST00000494626.6	TSL:1	c.-102+45593T>C		intron	N/A	ENSP00000436285.1

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44508 AN: 152012 Hom.: 7019 Cov.: 32

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.410

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.00328

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.287

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

GnomAD4 genome AF: 0.293 AC: 44560 AN: 152130 Hom.: 7030 Cov.: 32 AF XY: 0.288 AC XY: 21456 AN XY: 74378

African (AFR) AF: 0.372 AC: 15414 AN: 41482

American (AMR) AF: 0.242 AC: 3699 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 1163 AN: 3472

East Asian (EAS) AF: 0.00328 AC: 17 AN: 5178

South Asian (SAS) AF: 0.111 AC: 534 AN: 4816

European-Finnish (FIN) AF: 0.328 AC: 3466 AN: 10582

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.282 AC: 19206 AN: 67990

Other (OTH) AF: 0.284 AC: 599 AN: 2110

Alfa AF: 0.280 Hom.: 10646

Bravo AF: 0.291

Asia WGS AF: 0.0770 AC: 270 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.75
DANN	Benign	0.22
PhyloP100		-1.3
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: rs1152659; hg19: chr10-126776488;