rs893856

Variant names:

• chr10-125034998-G-A
• rs893856
• NM_001329.4:c.58+3999C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-125034998-G-A
• chr10-125034998-G-C
• chr10-125034998-G-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.58+3999C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,012 control chromosomes in the GnomAD database, including 2,894 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 0.19 (2894 hom., cov: 32)
• Consequence: CTBP2 NM_001329.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.759
• Publications: 12 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.262 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTBP2	NM_001329.4	MANE Select	c.58+3999C>T		intron	N/A	NP_001320.1	P56545-1
	CTBP2	NM_001083914.3		c.58+3999C>T		intron	N/A	NP_001077383.1	P56545-1
	CTBP2	NM_001290214.3		c.58+3999C>T		intron	N/A	NP_001277143.1	P56545-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTBP2	ENST00000337195.11	TSL:1 MANE Select	c.58+3999C>T		intron	N/A	ENSP00000338615.5	P56545-1
	CTBP2	ENST00000411419.7	TSL:1	c.58+3999C>T		intron	N/A	ENSP00000410474.2	P56545-1
	CTBP2	ENST00000494626.6	TSL:1	c.58+3999C>T		intron	N/A	ENSP00000436285.1	P56545-1

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28140 AN: 151894 Hom.: 2892 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.0449

Gnomad SAS AF: 0.0954

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.185 AC: 28173 AN: 152012 Hom.: 2894 Cov.: 32 AF XY: 0.187 AC XY: 13924 AN XY: 74314

African (AFR) AF: 0.235 AC: 9746 AN: 41434

American (AMR) AF: 0.269 AC: 4109 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 716 AN: 3472

East Asian (EAS) AF: 0.0452 AC: 234 AN: 5174

South Asian (SAS) AF: 0.0963 AC: 463 AN: 4806

European-Finnish (FIN) AF: 0.181 AC: 1920 AN: 10580

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.154 AC: 10493 AN: 67970

Other (OTH) AF: 0.195 AC: 411 AN: 2108

Alfa AF: 0.169 Hom.: 4094

Bravo AF: 0.195

Asia WGS AF: 0.104 AC: 365 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.28
DANN	Benign	0.35
PhyloP100		-0.76
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: rs893856; hg19: chr10-126723567;