NM_001012614.2:c.1222dupC

Variant names:

• chr4-1212307-T-TG
• NM_001012614.2:c.1222dupC

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001012614.2(CTBP1):​c.1222dupC​(p.His408ProfsTer15) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. H408H) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CTBP1 NM_001012614.2 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.22
• Publications: 0 publications found

Genes affected

CTBP1 (HGNC:2494): (C-terminal binding protein 1) This gene encodes a protein that binds to the C-terminus of adenovirus E1A proteins. This phosphoprotein is a transcriptional repressor and may play a role during cellular proliferation. This protein and the product of a second closely related gene, CTBP2, can dimerize. Both proteins can also interact with a polycomb group protein complex which participates in regulation of gene expression during development. Alternative splicing of transcripts from this gene results in multiple transcript variants. [provided by RefSeq, Jul 2008]

CTBP1-AS (HGNC:48337): (CTBP1 antisense RNA)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012614.2. 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
	CTBP1	NM_001012614.2	MANE Select	c.1222dupC	p.His408ProfsTer15	frameshift	Exon 10 of 10	NP_001012632.1	Q13363-2
	CTBP1	NM_001377186.1		c.1258dupC	p.His420ProfsTer15	frameshift	Exon 9 of 9	NP_001364115.1
	CTBP1	NM_001328.3		c.1255dupC	p.His419ProfsTer15	frameshift	Exon 9 of 9	NP_001319.1	X5D8Y5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTBP1	ENST00000382952.8	TSL:1 MANE Select	c.1222dupC	p.His408ProfsTer15	frameshift	Exon 10 of 10	ENSP00000372411.3	Q13363-2
	CTBP1	ENST00000290921.10	TSL:1	c.1255dupC	p.His419ProfsTer15	frameshift	Exon 9 of 9	ENSP00000290921.6	Q13363-1
	CTBP1-AS	ENST00000625256.1	TSL:1	n.784dupG		non_coding_transcript_exon	Exon 3 of 6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 45

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.2

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

hg19: chr4-1206095;