rs4962416

Positions:

• chr10-125008303-T-C

Variant summary

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

The NM_022802.3(CTBP2):​c.1679-4811A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 152,154 control chromosomes in the GnomAD database, including 4,414 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 0.23 (4414 hom., cov: 33)
• Consequence: CTBP2 NM_022802.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

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=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTBP2	NM_022802.3	c.1679-4811A>G		intron_variant		ENST00000309035.11	NP_073713.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTBP2	ENST00000309035.11	c.1679-4811A>G		intron_variant		1	NM_022802.3	ENSP00000311825

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34723 AN: 152038 Hom.: 4415 Cov.: 33

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.00967

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.255

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

GnomAD4 genome AF: 0.228 AC: 34731 AN: 152154 Hom.: 4414 Cov.: 33 AF XY: 0.223 AC XY: 16593 AN XY: 74388

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.225

Gnomad4 ASJ AF: 0.309

Gnomad4 EAS AF: 0.00969

Gnomad4 SAS AF: 0.316

Gnomad4 FIN AF: 0.149

Gnomad4 NFE AF: 0.282

Gnomad4 OTH AF: 0.253

Alfa AF: 0.275 Hom.: 11112

Bravo AF: 0.229

Asia WGS AF: 0.128 AC: 445 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	2.1
DANN	Benign	0.81

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: rs4962416; hg19: chr10-126696872; COSMIC: COSV58332887; COSMIC: COSV58332887;