rs4962418

Variant names:

• chr10-125008517-G-A
• rs4962418
• NM_001329.4:c.59-5025C>T

Variant summary

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

The NM_001329.4(CTBP2):​c.59-5025C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 152,180 control chromosomes in the GnomAD database, including 7,731 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 (7731 hom., cov: 34)
• Consequence: CTBP2 NM_001329.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.237
• Publications: 11 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=-1.03).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.371 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.59-5025C>T		intron	N/A	NP_001320.1
	CTBP2	NM_022802.3		c.1679-5025C>T		intron	N/A	NP_073713.2
	CTBP2	NM_001083914.3		c.59-5025C>T		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.59-5025C>T		intron	N/A	ENSP00000338615.5
	CTBP2	ENST00000309035.11	TSL:1	c.1679-5025C>T		intron	N/A	ENSP00000311825.6
	CTBP2	ENST00000411419.7	TSL:1	c.59-5025C>T		intron	N/A	ENSP00000410474.2

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45989 AN: 152062 Hom.: 7734 Cov.: 34

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.0191

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.344

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

GnomAD4 genome AF: 0.302 AC: 46004 AN: 152180 Hom.: 7731 Cov.: 34 AF XY: 0.299 AC XY: 22261 AN XY: 74394

African (AFR) AF: 0.184 AC: 7638 AN: 41526

American (AMR) AF: 0.365 AC: 5575 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 1386 AN: 3468

East Asian (EAS) AF: 0.0191 AC: 99 AN: 5180

South Asian (SAS) AF: 0.351 AC: 1691 AN: 4822

European-Finnish (FIN) AF: 0.278 AC: 2945 AN: 10582

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.375 AC: 25484 AN: 67992

Other (OTH) AF: 0.339 AC: 716 AN: 2112

Alfa AF: 0.358 Hom.: 15862

Bravo AF: 0.301

Asia WGS AF: 0.156 AC: 542 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	1.6
DANN	Benign	0.29
PhyloP100		0.24
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4962418; hg19: chr10-126697086;