rs718949

Variant names:

• chr10-125050460-A-G
• rs718949
• ENST00000337195.10:c.-101-11305T>C

Variant summary

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

The NM_001329.4(CTBP2):​c.-101-11305T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 152,214 control chromosomes in the GnomAD database, including 7,724 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 (7724 hom., cov: 33)
• Consequence: CTBP2 NM_001329.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.668

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTBP2	NM_001083914.3	c.-101-11305T>C		intron_variant	Intron 2 of 10		NP_001077383.1
CTBP2	NM_001290214.3	c.-101-11305T>C		intron_variant	Intron 2 of 10		NP_001277143.1
CTBP2	NM_001290215.3	c.-101-11305T>C		intron_variant	Intron 2 of 10		NP_001277144.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTBP2	ENST00000337195.10	c.-101-11305T>C		intron_variant	Intron 2 of 10	1		ENSP00000338615.5

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44871 AN: 152096 Hom.: 7703 Cov.: 33

Gnomad AFR AF: 0.482

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.0437

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.287

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.282

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

GnomAD4 genome AF: 0.295 AC: 44929 AN: 152214 Hom.: 7724 Cov.: 33 AF XY: 0.292 AC XY: 21748 AN XY: 74416

Gnomad4 AFR AF: 0.482

Gnomad4 AMR AF: 0.261

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.0438

Gnomad4 SAS AF: 0.279

Gnomad4 FIN AF: 0.208

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.278

Alfa AF: 0.240 Hom.: 6809

Bravo AF: 0.304

Asia WGS AF: 0.166 AC: 581 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	0.032
DANN	Benign	0.26
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs718949; hg19: chr10-126739029;