rs1254702

chr10-125120308-A-Cchr10-125120308-A-Gchr10-125120308-A-T

Variant summary

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

The ENST00000337195.10(CTBP2):c.-205-9215T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.886 in 152,286 control chromosomes in the GnomAD database, including 60,050 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 0.89 (60050 hom., cov: 34)
• Consequence: CTBP2 ENST00000337195.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.150

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.96 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTBP2	NM_001083914.3	c.-205-9215T>G		intron_variant
CTBP2	NM_001290214.3	c.-102+13204T>G		intron_variant
CTBP2	NM_001290215.3	c.-205-9215T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTBP2	ENST00000337195.10	c.-205-9215T>G		intron_variant		1		P1
CTBP2	ENST00000411419.7	c.-205-9215T>G		intron_variant		1		P1
CTBP2	ENST00000494626.6	c.-102+13204T>G		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.886 AC: 134806 AN: 152168 Hom.: 59998 Cov.: 34

Gnomad AFR AF: 0.968

Gnomad AMI AF: 0.799

Gnomad AMR AF: 0.883

Gnomad ASJ AF: 0.941

Gnomad EAS AF: 0.910

Gnomad SAS AF: 0.883

Gnomad FIN AF: 0.886

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.832

Gnomad OTH AF: 0.903

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

GnomAD4 genome AF: 0.886 AC: 134913 AN: 152286 Hom.: 60050 Cov.: 34 AF XY: 0.888 AC XY: 66140 AN XY: 74460

Gnomad4 AFR AF: 0.968

Gnomad4 AMR AF: 0.882

Gnomad4 ASJ AF: 0.941

Gnomad4 EAS AF: 0.911

Gnomad4 SAS AF: 0.883

Gnomad4 FIN AF: 0.886

Gnomad4 NFE AF: 0.832

Gnomad4 OTH AF: 0.904

Alfa AF: 0.850 Hom.: 56918

Bravo AF: 0.892

Asia WGS AF: 0.916 AC: 3185 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	4.8
Dann	Benign	0.76

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: rs1254702; hg19: chr10-126808877;