rs145193058

Variant names:

• chr4-1212257-C-A
• NM_001012614.2:c.1273G>T

Your query was ambiguous. Multiple possible variants found:

• chr4-1212257-C-A
• chr4-1212257-C-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.1273G>T​(p.Ala425Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000088 in 1,136,922 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A425D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.8e-7 (0 hom.)
• Consequence: CTBP1 NM_001012614.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13

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

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=0.07636246).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTBP1	NM_001012614.2	c.1273G>T	p.Ala425Ser	missense_variant	Exon 10 of 10	ENST00000382952.8	NP_001012632.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTBP1	ENST00000382952.8	c.1273G>T	p.Ala425Ser	missense_variant	Exon 10 of 10	1	NM_001012614.2	ENSP00000372411.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.80e-7 AC: 1 AN: 1136922 Hom.: 0 Cov.: 32 AF XY: 0.00000180 AC XY: 1 AN XY: 556830

Gnomad4 AFR exome AF: 0.0000454

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	10
DANN	Benign	0.71
DEOGEN2	Benign	0.34	.;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.80	T;T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.076	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	.;N
PrimateAI	Benign	0.44	T
PROVEAN	Benign	0.36	N;N
REVEL	Benign	0.27
Sift	Benign	0.057	T;T
Sift4G	Benign	0.42	T;T
Polyphen		0.0010	.;B
Vest4		0.069
MutPred		0.13		.;Gain of phosphorylation at A436 (P = 0.0084);
MVP		0.59
MPC		0.42
ClinPred		0.13	T
GERP RS		-9.4
Varity_R		0.028
gMVP		0.37

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: chr4-1206045;