rs893856

Positions:

• chr10-125034998-G-A

Variant summary

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

The NM_001329.4(CTBP2):​c.58+3999C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,012 control chromosomes in the GnomAD database, including 2,894 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 0.19 (2894 hom., cov: 32)
• Consequence: CTBP2 NM_001329.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.759

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]

CTBP2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTBP2	NM_001083914.3	c.58+3999C>T		intron_variant			NP_001077383.1
CTBP2	NM_001290214.3	c.58+3999C>T		intron_variant			NP_001277143.1
CTBP2	NM_001290215.3	c.58+3999C>T		intron_variant			NP_001277144.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTBP2	ENST00000337195.10	c.58+3999C>T		intron_variant		1		ENSP00000338615.5

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28140 AN: 151894 Hom.: 2892 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.0449

Gnomad SAS AF: 0.0954

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.185 AC: 28173 AN: 152012 Hom.: 2894 Cov.: 32 AF XY: 0.187 AC XY: 13924 AN XY: 74314

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.269

Gnomad4 ASJ AF: 0.206

Gnomad4 EAS AF: 0.0452

Gnomad4 SAS AF: 0.0963

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.154

Gnomad4 OTH AF: 0.195

Alfa AF: 0.166 Hom.: 3128

Bravo AF: 0.195

Asia WGS AF: 0.104 AC: 365 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.28
DANN	Benign	0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs893856; hg19: chr10-126723567;