10-125104229-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000337195.10(CTBP2):c.-102+6761G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0628 in 152,224 control chromosomes in the GnomAD database, including 295 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 0.063 (295 hom., cov: 33)
• Consequence: CTBP2 ENST00000337195.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.209

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTBP2	NM_001083914.3	c.-102+6761G>A		intron_variant
CTBP2	NM_001290214.3	c.-102+29283G>A		intron_variant
CTBP2	NM_001290215.3	c.-102+6761G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTBP2	ENST00000337195.10	c.-102+6761G>A		intron_variant		1		P1
CTBP2	ENST00000411419.7	c.-102+6761G>A		intron_variant		1		P1
CTBP2	ENST00000494626.6	c.-102+29283G>A		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.0629 AC: 9564 AN: 152106 Hom.: 295 Cov.: 33

Gnomad AFR AF: 0.0558

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0484

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.0441

Gnomad SAS AF: 0.0268

Gnomad FIN AF: 0.0365

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0749

Gnomad OTH AF: 0.0629

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

GnomAD4 genome AF: 0.0628 AC: 9563 AN: 152224 Hom.: 295 Cov.: 33 AF XY: 0.0590 AC XY: 4391 AN XY: 74422

Gnomad4 AFR AF: 0.0557

Gnomad4 AMR AF: 0.0483

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.0442

Gnomad4 SAS AF: 0.0264

Gnomad4 FIN AF: 0.0365

Gnomad4 NFE AF: 0.0749

Gnomad4 OTH AF: 0.0617

Alfa AF: 0.0601 Hom.: 164

Bravo AF: 0.0637

Asia WGS AF: 0.0440 AC: 153 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.7
Dann	Benign	0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs17643974; hg19: chr10-126792798;