NM_001329.4:c.59-4811A>G

Variant names:

• chr10-125008303-T-C
• rs4962416
• NM_001329.4:c.59-4811A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001329.4(CTBP2):​c.59-4811A>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_001329.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 126 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001329.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTBP2	NM_001329.4	MANE Select	c.59-4811A>G		intron	N/A	NP_001320.1
	CTBP2	NM_022802.3		c.1679-4811A>G		intron	N/A	NP_073713.2
	CTBP2	NM_001083914.3		c.59-4811A>G		intron	N/A	NP_001077383.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTBP2	ENST00000337195.11	TSL:1 MANE Select	c.59-4811A>G		intron	N/A	ENSP00000338615.5
	CTBP2	ENST00000309035.11	TSL:1	c.1679-4811A>G		intron	N/A	ENSP00000311825.6
	CTBP2	ENST00000411419.7	TSL:1	c.59-4811A>G		intron	N/A	ENSP00000410474.2

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

African (AFR) AF: 0.167 AC: 6932 AN: 41526

American (AMR) AF: 0.225 AC: 3437 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1072 AN: 3470

East Asian (EAS) AF: 0.00969 AC: 50 AN: 5160

South Asian (SAS) AF: 0.316 AC: 1525 AN: 4820

European-Finnish (FIN) AF: 0.149 AC: 1577 AN: 10596

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.282 AC: 19158 AN: 67974

Other (OTH) AF: 0.253 AC: 535 AN: 2116

Alfa AF: 0.266 Hom.: 22782

Bravo AF: 0.229

Asia WGS AF: 0.128 AC: 445 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.1
DANN	Benign	0.81
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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