rs1715873

chr10-125137034-A-Gchr10-125137034-A-T

Variant summary

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

The ENST00000337195.10(CTBP2):c.-206+23285T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.842 in 152,208 control chromosomes in the GnomAD database, including 54,091 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 0.84 (54091 hom., cov: 33)
• Consequence: CTBP2 ENST00000337195.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTBP2	NM_001083914.3	c.-206+23793T>C		intron_variant
CTBP2	NM_001290214.3	c.-202-3422T>C		intron_variant
CTBP2	NM_001290215.3	c.-206+21601T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTBP2	ENST00000337195.10	c.-206+23285T>C		intron_variant		1		P1
CTBP2	ENST00000411419.7	c.-206+23793T>C		intron_variant		1		P1
CTBP2	ENST00000494626.6	c.-202-3422T>C		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.842 AC: 128108 AN: 152090 Hom.: 54060 Cov.: 33

Gnomad AFR AF: 0.888

Gnomad AMI AF: 0.791

Gnomad AMR AF: 0.844

Gnomad ASJ AF: 0.931

Gnomad EAS AF: 0.902

Gnomad SAS AF: 0.838

Gnomad FIN AF: 0.807

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.810

Gnomad OTH AF: 0.870

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

GnomAD4 genome AF: 0.842 AC: 128191 AN: 152208 Hom.: 54091 Cov.: 33 AF XY: 0.843 AC XY: 62691 AN XY: 74400

Gnomad4 AFR AF: 0.888

Gnomad4 AMR AF: 0.843

Gnomad4 ASJ AF: 0.931

Gnomad4 EAS AF: 0.903

Gnomad4 SAS AF: 0.837

Gnomad4 FIN AF: 0.807

Gnomad4 NFE AF: 0.810

Gnomad4 OTH AF: 0.871

Alfa AF: 0.758 Hom.: 2212

Bravo AF: 0.849

Asia WGS AF: 0.888 AC: 3088 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.14
Dann	Benign	0.23

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: rs1715873; hg19: chr10-126825603;