rs76804352

Variant names:

• chr10-124993314-C-A
• rs76804352
• NM_001329.4:c.927G>T

Your query was ambiguous. Multiple possible variants found:

• chr10-124993314-C-A
• chr10-124993314-C-T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_001329.4(CTBP2):​c.927G>T​(p.Pro309Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000481 in 1,456,396 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P309P) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: CTBP2 NM_001329.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.20
• Publications: 0 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP7: Synonymous conserved (PhyloP=-6.2 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 7 AD gene.

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.927G>T	p.Pro309Pro	synonymous	Exon 9 of 11	NP_001320.1	P56545-1
	CTBP2	NM_022802.3		c.2547G>T	p.Pro849Pro	synonymous	Exon 7 of 9	NP_073713.2	P56545-2
	CTBP2	NM_001363508.2		c.1131G>T	p.Pro377Pro	synonymous	Exon 7 of 9	NP_001350437.1	P56545-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTBP2	ENST00000337195.11	TSL:1 MANE Select	c.927G>T	p.Pro309Pro	synonymous	Exon 9 of 11	ENSP00000338615.5	P56545-1
	CTBP2	ENST00000309035.11	TSL:1	c.2547G>T	p.Pro849Pro	synonymous	Exon 7 of 9	ENSP00000311825.6	P56545-2
	CTBP2	ENST00000334808.10	TSL:1	c.1131G>T	p.Pro377Pro	synonymous	Exon 7 of 9	ENSP00000357816.5	P56545-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000481 AC: 7 AN: 1456396 Hom.: 0 Cov.: 32 AF XY: 0.00000276 AC XY: 2 AN XY: 723530

African (AFR) AF: 0.00 AC: 0 AN: 33382

American (AMR) AF: 0.00 AC: 0 AN: 44650

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26064

East Asian (EAS) AF: 0.00 AC: 0 AN: 39548

South Asian (SAS) AF: 0.00 AC: 0 AN: 86002

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53312

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.00000632 AC: 7 AN: 1107614

Other (OTH) AF: 0.00 AC: 0 AN: 60084

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.50
DANN	Benign	0.86
PhyloP100		-6.2

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: rs76804352; hg19: chr10-126681883;