rs7077275

Variant names:

• chr10-125008641-T-C
• rs7077275
• NM_001329.4:c.59-5149A>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.59-5149A>G 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 152,248 control chromosomes in the GnomAD database, including 7,743 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 (7743 hom., cov: 34)
• Consequence: CTBP2 NM_001329.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.846
• Publications: 15 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=-0.89).
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTBP2	NM_001329.4	MANE Select	c.59-5149A>G		intron	N/A	NP_001320.1	P56545-1
	CTBP2	NM_022802.3		c.1679-5149A>G		intron	N/A	NP_073713.2	P56545-2
	CTBP2	NM_001083914.3		c.59-5149A>G		intron	N/A	NP_001077383.1	P56545-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTBP2	ENST00000337195.11	TSL:1 MANE Select	c.59-5149A>G		intron	N/A	ENSP00000338615.5	P56545-1
	CTBP2	ENST00000309035.11	TSL:1	c.1679-5149A>G		intron	N/A	ENSP00000311825.6	P56545-2
	CTBP2	ENST00000411419.7	TSL:1	c.59-5149A>G		intron	N/A	ENSP00000410474.2	P56545-1

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46025 AN: 152130 Hom.: 7746 Cov.: 34

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.0190

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.279

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: 46040 AN: 152248 Hom.: 7743 Cov.: 34 AF XY: 0.299 AC XY: 22288 AN XY: 74434

African (AFR) AF: 0.184 AC: 7658 AN: 41542

American (AMR) AF: 0.365 AC: 5579 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 1386 AN: 3472

East Asian (EAS) AF: 0.0191 AC: 99 AN: 5186

South Asian (SAS) AF: 0.352 AC: 1698 AN: 4830

European-Finnish (FIN) AF: 0.279 AC: 2950 AN: 10592

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

European-Non Finnish (NFE) AF: 0.375 AC: 25482 AN: 68004

Other (OTH) AF: 0.339 AC: 718 AN: 2116

Alfa AF: 0.362 Hom.: 8556

Bravo AF: 0.301

Asia WGS AF: 0.156 AC: 543 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.4
DANN	Benign	0.82
PhyloP100		-0.85
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs7077275; hg19: chr10-126697210;