NM_001012614.2:c.1273G>A

Variant names:

• chr4-1212257-C-T
• rs145193058
• NM_001012614.2:c.1273G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001012614.2(CTBP1):​c.1273G>A​(p.Ala425Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000266 in 1,279,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). 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: 𝑓 0.000049 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000024 (0 hom.)
• Consequence: CTBP1 NM_001012614.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.13
• Publications: 1 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.030695349).
• BP6: Variant 4-1212257-C-T is Benign according to our data. Variant chr4-1212257-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3341776.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 7 AD gene.

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.1273G>A	p.Ala425Thr	missense	Exon 10 of 10	NP_001012632.1	Q13363-2
	CTBP1	NM_001377186.1		c.1309G>A	p.Ala437Thr	missense	Exon 9 of 9	NP_001364115.1
	CTBP1	NM_001328.3		c.1306G>A	p.Ala436Thr	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.1273G>A	p.Ala425Thr	missense	Exon 10 of 10	ENSP00000372411.3	Q13363-2
	CTBP1	ENST00000290921.10	TSL:1	c.1306G>A	p.Ala436Thr	missense	Exon 9 of 9	ENSP00000290921.6	Q13363-1
	CTBP1-AS	ENST00000625256.1	TSL:1	n.730C>T		non_coding_transcript_exon	Exon 3 of 6

Frequencies

GnomAD3 genomes AF: 0.0000493 AC: 7 AN: 142120 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000503

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000248

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00325

Gnomad NFE AF: 0.0000464

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000582 AC: 8 AN: 137454 AF XY: 0.0000133

Gnomad AFR exome AF: 0.000147

Gnomad AMR exome AF: 0.000100

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000870

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000237 AC: 27 AN: 1136922 Hom.: 0 Cov.: 32 AF XY: 0.0000216 AC XY: 12 AN XY: 556830

African (AFR) AF: 0.00 AC: 0 AN: 22018

American (AMR) AF: 0.0000425 AC: 1 AN: 23502

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14744

East Asian (EAS) AF: 0.00 AC: 0 AN: 10934

South Asian (SAS) AF: 0.00 AC: 0 AN: 73276

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29142

Middle Eastern (MID) AF: 0.000258 AC: 1 AN: 3876

European-Non Finnish (NFE) AF: 0.0000250 AC: 23 AN: 918388

Other (OTH) AF: 0.0000487 AC: 2 AN: 41042

GnomAD4 genome AF: 0.0000492 AC: 7 AN: 142276 Hom.: 0 Cov.: 32 AF XY: 0.0000578 AC XY: 4 AN XY: 69162

African (AFR) AF: 0.0000502 AC: 2 AN: 39872

American (AMR) AF: 0.00 AC: 0 AN: 14480

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3320

East Asian (EAS) AF: 0.000248 AC: 1 AN: 4030

South Asian (SAS) AF: 0.00 AC: 0 AN: 3850

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8898

Middle Eastern (MID) AF: 0.00350 AC: 1 AN: 286

European-Non Finnish (NFE) AF: 0.0000464 AC: 3 AN: 64654

Other (OTH) AF: 0.00 AC: 0 AN: 2026

Alfa AF: 0.0000886 Hom.: 0

Bravo AF: 0.0000340

ESP6500AA AF: 0.000232 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000169 AC: 2

ClinVar

ClinVar submissions

Significance: Likely benign

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	Benign	0.061
BayesDel_addAF	Benign	-0.062	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	13
DANN	Benign	0.89
DEOGEN2	Benign	0.35	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.82	T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.031	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N
PhyloP100		1.1
PrimateAI	Benign	0.45	T
PROVEAN	Benign	0.10	N
REVEL	Uncertain	0.32
Sift	Benign	0.16	T
Sift4G	Benign	0.45	T
Polyphen		0.0	B
Vest4		0.025
MVP		0.55
MPC		0.45
ClinPred		0.015	T
GERP RS		-9.4
Varity_R		0.022
gMVP		0.39
Mutation Taster		=94/6	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

dbSNP: rs145193058; hg19: chr4-1206045;