rs748609943

Variant names:

• chr4-1212284-C-G
• NM_001012614.2:c.1246G>C

Your query was ambiguous. Multiple possible variants found:

• chr4-1212284-C-G
• chr4-1212284-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.1246G>C​(p.Val416Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 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. V416I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CTBP1 NM_001012614.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.53

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=0.13223633).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTBP1	NM_001012614.2	c.1246G>C	p.Val416Leu	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.1246G>C	p.Val416Leu	missense_variant	Exon 10 of 10	1	NM_001012614.2	ENSP00000372411.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 868376 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 431820

Gnomad4 AFR exome AF: 0.00

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	0.073
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	22
DANN	Benign	0.79
DEOGEN2	Benign	0.34	.;T
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.65	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Pathogenic	0.46	D
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	-0.34	.;N
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.27	N;N
REVEL	Uncertain	0.32
Sift	Benign	0.15	T;T
Sift4G	Benign	0.27	T;T
Polyphen		0.0	.;B
Vest4		0.34
MutPred		0.068		.;Loss of methylation at K428 (P = 0.0465);
MVP		0.39
MPC		0.46
ClinPred		0.11	T
GERP RS		0.94
Varity_R		0.058
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: chr4-1206072;