4-1212256-G-T

Position:

• chr4-1212256-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001012614.2(CTBP1):​c.1274C>A​(p.Ala425Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000022 in 1,366,440 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: CTBP1 NM_001012614.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.84

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:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22686446).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTBP1	NM_001012614.2	c.1274C>A	p.Ala425Asp	missense_variant	10/10	ENST00000382952.8	NP_001012632.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTBP1	ENST00000382952.8	c.1274C>A	p.Ala425Asp	missense_variant	10/10	1	NM_001012614.2	ENSP00000372411.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000220 AC: 3 AN: 1366440 Hom.: 0 Cov.: 32 AF XY: 0.00000148 AC XY: 1 AN XY: 674140

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000312

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000188

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.00053	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	23
DANN	Benign	0.94
DEOGEN2	Benign	0.41	.;T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.25
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Pathogenic	0.73	D
MetaRNN	Benign	0.23	T;T
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Benign	0.0	.;N
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.37	N;N
REVEL	Uncertain	0.31
Sift	Uncertain	0.0040	D;D
Sift4G	Uncertain	0.033	D;D
Polyphen		0.034	.;B
Vest4		0.12
MutPred		0.16		.;Loss of helix (P = 0.1706);
MVP		0.49
MPC		0.71
ClinPred		0.45	T
GERP RS		4.7
Varity_R		0.16
gMVP		0.49

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-1206044;