chr4-1212298-G-A

Variant names:

• chr4-1212298-G-A
• NM_001012614.2:c.1232C>T

Variant summary

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

The NM_001012614.2(CTBP1):​c.1232C>T​(p.Ser411Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000084 in 1,190,924 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.4e-7 (0 hom.)
• Consequence: CTBP1 NM_001012614.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.13
• 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.1232C>T	p.Ser411Phe	missense	Exon 10 of 10	NP_001012632.1	Q13363-2
	CTBP1	NM_001377186.1		c.1268C>T	p.Ser423Phe	missense	Exon 9 of 9	NP_001364115.1
	CTBP1	NM_001328.3		c.1265C>T	p.Ser422Phe	missense	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.1232C>T	p.Ser411Phe	missense	Exon 10 of 10	ENSP00000372411.3	Q13363-2
	CTBP1	ENST00000290921.10	TSL:1	c.1265C>T	p.Ser422Phe	missense	Exon 9 of 9	ENSP00000290921.6	Q13363-1
	CTBP1-AS	ENST00000625256.1	TSL:1	n.771G>A		non_coding_transcript_exon	Exon 3 of 6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.40e-7 AC: 1 AN: 1190924 Hom.: 0 Cov.: 43 AF XY: 0.00 AC XY: 0 AN XY: 590690

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 24086

American (AMR) AF: 0.0000350 AC: 1 AN: 28592

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19260

East Asian (EAS) AF: 0.00 AC: 0 AN: 24246

South Asian (SAS) AF: 0.00 AC: 0 AN: 74696

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38256

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4466

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 930110

Other (OTH) AF: 0.00 AC: 0 AN: 47212

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

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
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.65	D
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Pathogenic	0.86	D
MetaRNN	Uncertain	0.53	D
MetaSVM	Uncertain	0.39	D
MutationAssessor	Benign	1.8	L
PhyloP100		7.1
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-2.5	D
REVEL	Uncertain	0.46
Sift	Uncertain	0.010	D
Sift4G	Benign	0.31	T
Polyphen		1.0	D
Vest4		0.35
MutPred		0.20		Loss of glycosylation at S422 (P = 0.0069)
MVP		0.72
MPC		1.4
ClinPred		0.93	D
GERP RS		3.8
Varity_R		0.39
gMVP		0.71
Mutation Taster		=72/28	polymorphism

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

hg19: chr4-1206086;