rs4962418

Positions:

• chr10-125008517-G-A

Variant summary

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

The NM_022802.3(CTBP2):​c.1679-5025C>T 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 152,180 control chromosomes in the GnomAD database, including 7,731 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 (7731 hom., cov: 34)
• Consequence: CTBP2 NM_022802.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.237

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=-1.03).
• 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.1679-5025C>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.1679-5025C>T		intron_variant		1	NM_022802.3	ENSP00000311825

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45989 AN: 152062 Hom.: 7734 Cov.: 34

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.0191

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.278

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: 46004 AN: 152180 Hom.: 7731 Cov.: 34 AF XY: 0.299 AC XY: 22261 AN XY: 74394

Gnomad4 AFR AF: 0.184

Gnomad4 AMR AF: 0.365

Gnomad4 ASJ AF: 0.400

Gnomad4 EAS AF: 0.0191

Gnomad4 SAS AF: 0.351

Gnomad4 FIN AF: 0.278

Gnomad4 NFE AF: 0.375

Gnomad4 OTH AF: 0.339

Alfa AF: 0.365 Hom.: 11269

Bravo AF: 0.301

Asia WGS AF: 0.156 AC: 542 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	1.6
DANN	Benign	0.29

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: rs4962418; hg19: chr10-126697086;