rs1561589

Positions:

• chr10-125007104-G-A
• chr10-125007104-G-C

Variant summary

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

The NM_022802.3(CTBP2):​c.1679-3612C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 152,094 control chromosomes in the GnomAD database, including 13,986 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 0.41 (13986 hom., cov: 34)
• Consequence: CTBP2 NM_022802.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTBP2	NM_022802.3	c.1679-3612C>T		intron_variant		ENST00000309035.11	NP_073713.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTBP2	ENST00000309035.11	c.1679-3612C>T		intron_variant		1	NM_022802.3	ENSP00000311825

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62698 AN: 151976 Hom.: 13969 Cov.: 34

Gnomad AFR AF: 0.582

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.406

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

GnomAD4 genome AF: 0.413 AC: 62763 AN: 152094 Hom.: 13986 Cov.: 34 AF XY: 0.405 AC XY: 30133 AN XY: 74358

Gnomad4 AFR AF: 0.582

Gnomad4 AMR AF: 0.391

Gnomad4 ASJ AF: 0.352

Gnomad4 EAS AF: 0.270

Gnomad4 SAS AF: 0.422

Gnomad4 FIN AF: 0.224

Gnomad4 NFE AF: 0.358

Gnomad4 OTH AF: 0.402

Alfa AF: 0.379 Hom.: 18172

Bravo AF: 0.433

Asia WGS AF: 0.300 AC: 1042 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.55

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: rs1561589; hg19: chr10-126695673;