rs7077275

Positions:

• chr10-125008641-T-C

Variant summary

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

The ENST00000309035.11(CTBP2):​c.1679-5149A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 152,248 control chromosomes in the GnomAD database, including 7,743 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 0.30 (7743 hom., cov: 34)
• Consequence: CTBP2 ENST00000309035.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.846

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTBP2	NM_022802.3	c.1679-5149A>G		intron_variant		ENST00000309035.11	NP_073713.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTBP2	ENST00000309035.11	c.1679-5149A>G		intron_variant		1	NM_022802.3	ENSP00000311825

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46025 AN: 152130 Hom.: 7746 Cov.: 34

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.0190

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.344

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

GnomAD4 genome AF: 0.302 AC: 46040 AN: 152248 Hom.: 7743 Cov.: 34 AF XY: 0.299 AC XY: 22288 AN XY: 74434

Gnomad4 AFR AF: 0.184

Gnomad4 AMR AF: 0.365

Gnomad4 ASJ AF: 0.399

Gnomad4 EAS AF: 0.0191

Gnomad4 SAS AF: 0.352

Gnomad4 FIN AF: 0.279

Gnomad4 NFE AF: 0.375

Gnomad4 OTH AF: 0.339

Alfa AF: 0.362 Hom.: 5955

Bravo AF: 0.301

Asia WGS AF: 0.156 AC: 543 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.4
DANN	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs7077275; hg19: chr10-126697210;