chr10-125019312-C-T

Position:

• chr10-125019312-C-T

Variant summary

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

The NM_022802.3(CTBP2):​c.1678+6770G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 151,912 control chromosomes in the GnomAD database, including 11,329 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 0.38 (11329 hom., cov: 32)
• Consequence: CTBP2 NM_022802.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36

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=-1.04).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTBP2	NM_022802.3	c.1678+6770G>A		intron_variant		ENST00000309035.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTBP2	ENST00000309035.11	c.1678+6770G>A		intron_variant		1	NM_022802.3

Frequencies

GnomAD3 genomes AF: 0.382 AC: 57951 AN: 151794 Hom.: 11320 Cov.: 32

Gnomad AFR AF: 0.436

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.385

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

GnomAD4 genome AF: 0.382 AC: 57995 AN: 151912 Hom.: 11329 Cov.: 32 AF XY: 0.378 AC XY: 28067 AN XY: 74220

Gnomad4 AFR AF: 0.435

Gnomad4 AMR AF: 0.443

Gnomad4 ASJ AF: 0.356

Gnomad4 EAS AF: 0.269

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.327

Gnomad4 NFE AF: 0.365

Gnomad4 OTH AF: 0.379

Alfa AF: 0.369 Hom.: 21003

Bravo AF: 0.398

Asia WGS AF: 0.239 AC: 830 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.036
DANN	Benign	0.72

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: rs10901850; hg19: chr10-126707881;