rs369652853

Variant names:

• chr4-1212324-A-T
• rs369652853
• NM_001012614.2:c.1206T>A

Your query was ambiguous. Multiple possible variants found:

• chr4-1212324-A-T
• chr4-1212324-A-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4 BP6_Very_Strong BP7 BS2

The NM_001012614.2(CTBP1):​c.1206T>A​(p.Pro402Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000793 in 1,506,040 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 Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00062 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00081 (0 hom.)
• Consequence: CTBP1 NM_001012614.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.728
• 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.186).
• BP6: Variant 4-1212324-A-T is Benign according to our data. Variant chr4-1212324-A-T is described in ClinVar as Benign. ClinVar VariationId is 750794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.728 with no splicing effect.
• BS2: High AC in GnomAd4 at 94 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.1206T>A	p.Pro402Pro	synonymous	Exon 10 of 10	NP_001012632.1	Q13363-2
	CTBP1	NM_001377186.1		c.1242T>A	p.Pro414Pro	synonymous	Exon 9 of 9	NP_001364115.1
	CTBP1	NM_001328.3		c.1239T>A	p.Pro413Pro	synonymous	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.1206T>A	p.Pro402Pro	synonymous	Exon 10 of 10	ENSP00000372411.3	Q13363-2
	CTBP1	ENST00000290921.10	TSL:1	c.1239T>A	p.Pro413Pro	synonymous	Exon 9 of 9	ENSP00000290921.6	Q13363-1
	CTBP1-AS	ENST00000625256.1	TSL:1	n.797A>T		non_coding_transcript_exon	Exon 3 of 6

Frequencies

GnomAD3 genomes AF: 0.000619 AC: 94 AN: 151904 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000285

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00122

Gnomad OTH AF: 0.000480

GnomAD2 exomes AF: 0.000448 AC: 61 AN: 136246 AF XY: 0.000475

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000303

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000195

Gnomad NFE exome AF: 0.000855

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000812 AC: 1100 AN: 1354018 Hom.: 0 Cov.: 34 AF XY: 0.000765 AC XY: 512 AN XY: 669034

African (AFR) AF: 0.0000723 AC: 2 AN: 27664

American (AMR) AF: 0.000183 AC: 5 AN: 27382

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22482

East Asian (EAS) AF: 0.00 AC: 0 AN: 32630

South Asian (SAS) AF: 0.0000134 AC: 1 AN: 74538

European-Finnish (FIN) AF: 0.000308 AC: 15 AN: 48774

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4986

European-Non Finnish (NFE) AF: 0.000999 AC: 1059 AN: 1059774

Other (OTH) AF: 0.000323 AC: 18 AN: 55788

GnomAD4 genome AF: 0.000618 AC: 94 AN: 152022 Hom.: 0 Cov.: 33 AF XY: 0.000551 AC XY: 41 AN XY: 74366

African (AFR) AF: 0.000120 AC: 5 AN: 41534

American (AMR) AF: 0.000131 AC: 2 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.00 AC: 0 AN: 4806

European-Finnish (FIN) AF: 0.000285 AC: 3 AN: 10542

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00122 AC: 83 AN: 67920

Other (OTH) AF: 0.000475 AC: 1 AN: 2104

Alfa AF: 0.000494 Hom.: 0

Bravo AF: 0.000416

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	CTBP1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.76
DANN	Benign	0.59
PhyloP100		-0.73
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs369652853; hg19: chr4-1206112;