10-125162224-C-G

Position:

• chr10-125162224-C-G

Variant summary

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

The XM_047424671.1(CTBP2):​c.-335+104G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 152,094 control chromosomes in the GnomAD database, including 17,224 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 0.47 (17224 hom., cov: 33)
• Consequence: CTBP2 XM_047424671.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.367

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTBP2	XM_047424671.1	c.-335+104G>C		intron_variant			XP_047280627.1
		n.125162224C>G		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70724 AN: 151976 Hom.: 17198 Cov.: 33

Gnomad AFR AF: 0.594

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.457

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

GnomAD4 genome AF: 0.466 AC: 70805 AN: 152094 Hom.: 17224 Cov.: 33 AF XY: 0.462 AC XY: 34361 AN XY: 74330

Gnomad4 AFR AF: 0.594

Gnomad4 AMR AF: 0.529

Gnomad4 ASJ AF: 0.470

Gnomad4 EAS AF: 0.206

Gnomad4 SAS AF: 0.449

Gnomad4 FIN AF: 0.341

Gnomad4 NFE AF: 0.414

Gnomad4 OTH AF: 0.461

Alfa AF: 0.267 Hom.: 549

Bravo AF: 0.485

Asia WGS AF: 0.391 AC: 1356 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.3
DANN	Benign	0.75

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1057234; hg19: chr10-126850793;