chr10-125162224-C-G

Variant names:

• chr10-125162224-C-G
• rs1057234
• XM_047424671.1:c.-335+104G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

ENSG00000282787 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CTBP2	XM_047424671.1	c.-335+104G>C		intron_variant	Intron 1 of 11		XP_047280627.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000282787	ENST00000631930.1	n.-155C>G		upstream_gene_variant		6

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

African (AFR) AF: 0.594 AC: 24659 AN: 41484

American (AMR) AF: 0.529 AC: 8089 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.470 AC: 1630 AN: 3470

East Asian (EAS) AF: 0.206 AC: 1060 AN: 5152

South Asian (SAS) AF: 0.449 AC: 2166 AN: 4824

European-Finnish (FIN) AF: 0.341 AC: 3605 AN: 10572

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.414 AC: 28150 AN: 67976

Other (OTH) AF: 0.461 AC: 975 AN: 2114

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
PhyloP100		-0.37

Splicing

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

Other links and lift over

dbSNP: rs1057234; hg19: chr10-126850793;