rs12761801

Positions:

• chr10-125084412-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+26578G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0623 in 152,272 control chromosomes in the GnomAD database, including 306 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 0.062 (306 hom., cov: 32)
• Consequence: CTBP2 ENST00000337195.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.439

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=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0908 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTBP2	NM_001083914.3	c.-102+26578G>A		intron_variant			NP_001077383.1
CTBP2	NM_001290214.3	c.-101-45257G>A		intron_variant			NP_001277143.1
CTBP2	NM_001290215.3	c.-102+26578G>A		intron_variant			NP_001277144.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTBP2	ENST00000337195.10	c.-102+26578G>A		intron_variant		1		ENSP00000338615	P1
CTBP2	ENST00000411419.7	c.-102+26578G>A		intron_variant		1		ENSP00000410474	P1
CTBP2	ENST00000494626.6	c.-101-45257G>A		intron_variant		1		ENSP00000436285	P1

Frequencies

GnomAD3 genomes AF: 0.0623 AC: 9485 AN: 152152 Hom.: 305 Cov.: 32

Gnomad AFR AF: 0.0465

Gnomad AMI AF: 0.0242

Gnomad AMR AF: 0.0464

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.0975

Gnomad SAS AF: 0.0330

Gnomad FIN AF: 0.0926

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0679

Gnomad OTH AF: 0.0670

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

GnomAD4 genome AF: 0.0623 AC: 9494 AN: 152272 Hom.: 306 Cov.: 32 AF XY: 0.0620 AC XY: 4614 AN XY: 74460

Gnomad4 AFR AF: 0.0464

Gnomad4 AMR AF: 0.0465

Gnomad4 ASJ AF: 0.114

Gnomad4 EAS AF: 0.0978

Gnomad4 SAS AF: 0.0330

Gnomad4 FIN AF: 0.0926

Gnomad4 NFE AF: 0.0680

Gnomad4 OTH AF: 0.0677

Alfa AF: 0.0648 Hom.: 299

Bravo AF: 0.0597

Asia WGS AF: 0.0780 AC: 269 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	11
DANN	Benign	0.95

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

Publications

LitVar

Other links and lift over

dbSNP: rs12761801; hg19: chr10-126772981;