rs1253462797

Variant names:

• chr4-1212335-C-A
• rs1253462797
• NM_001012614.2:c.1195G>T

Your query was ambiguous. Multiple possible variants found:

• chr4-1212335-C-A
• chr4-1212335-C-T

Variant summary

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

The NM_001012614.2(CTBP1):​c.1195G>T​(p.Gly399Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000731 in 1,367,972 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. G399S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: CTBP1 NM_001012614.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.32
• 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.1195G>T	p.Gly399Cys	missense	Exon 10 of 10	NP_001012632.1	Q13363-2
	CTBP1	NM_001377186.1		c.1231G>T	p.Gly411Cys	missense	Exon 9 of 9	NP_001364115.1
	CTBP1	NM_001328.3		c.1228G>T	p.Gly410Cys	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.1195G>T	p.Gly399Cys	missense	Exon 10 of 10	ENSP00000372411.3	Q13363-2
	CTBP1	ENST00000290921.10	TSL:1	c.1228G>T	p.Gly410Cys	missense	Exon 9 of 9	ENSP00000290921.6	Q13363-1
	CTBP1-AS	ENST00000625256.1	TSL:1	n.808C>A		non_coding_transcript_exon	Exon 3 of 6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.31e-7 AC: 1 AN: 1367972 Hom.: 0 Cov.: 34 AF XY: 0.00000148 AC XY: 1 AN XY: 675862

⚠️ 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: 27982

American (AMR) AF: 0.00 AC: 0 AN: 28098

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22660

East Asian (EAS) AF: 0.00 AC: 0 AN: 33042

South Asian (SAS) AF: 0.00 AC: 0 AN: 75084

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49040

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5042

European-Non Finnish (NFE) AF: 9.34e-7 AC: 1 AN: 1070704

Other (OTH) AF: 0.00 AC: 0 AN: 56320

⚠️ 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.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Uncertain	0.025	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.71	D
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.19
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.79	T
M_CAP	Pathogenic	0.61	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.1	L
PhyloP100		3.3
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-2.4	N
REVEL	Uncertain	0.34
Sift	Uncertain	0.028	D
Sift4G	Uncertain	0.018	D
Polyphen		0.85	P
Vest4		0.43
MutPred		0.17		Loss of loop (P = 0.1242)
MVP		0.79
MPC		0.91
ClinPred		0.85	D
GERP RS		3.4
Varity_R		0.22
gMVP		0.48
Mutation Taster		=84/16	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

dbSNP: rs1253462797; hg19: chr4-1206123;