4-1249829-T-C

Position:

• chr4-1249829-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001377190.1(CTBP1):​c.-369A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 207,954 control chromosomes in the GnomAD database, including 29,545 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.52 (20906 hom., cov: 35)
  • Exomes 𝑓: 0.54 (8639 hom.)
• Consequence: CTBP1 NM_001377190.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.959

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-DT (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTBP1	NM_001377190.1	c.-369A>G		5_prime_UTR_premature_start_codon_gain_variant	1/10		NP_001364119.1
CTBP1	NM_001377193.1	c.-369A>G		5_prime_UTR_premature_start_codon_gain_variant	1/10		NP_001364122.1
CTBP1	NM_001377190.1	c.-369A>G		5_prime_UTR_variant	1/10		NP_001364119.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTBP1	ENST00000506180.5	c.-198A>G		5_prime_UTR_premature_start_codon_gain_variant	1/5	5		ENSP00000424684.2
CTBP1	ENST00000515399.5	c.-369A>G		5_prime_UTR_premature_start_codon_gain_variant	1/5	3		ENSP00000425053.1
CTBP1	ENST00000506180.5	c.-198A>G		5_prime_UTR_variant	1/5	5		ENSP00000424684.2

Frequencies

GnomAD3 genomes AF: 0.520 AC: 79058 AN: 152054 Hom.: 20879 Cov.: 35

Gnomad AFR AF: 0.439

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.607

Gnomad ASJ AF: 0.543

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.639

Gnomad FIN AF: 0.590

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.516

Gnomad OTH AF: 0.478

GnomAD4 exome AF: 0.539 AC: 30088 AN: 55782 Hom.: 8639 Cov.: 0 AF XY: 0.555 AC XY: 19360 AN XY: 34856

Gnomad4 AFR exome AF: 0.388

Gnomad4 AMR exome AF: 0.675

Gnomad4 ASJ exome AF: 0.522

Gnomad4 EAS exome AF: 0.636

Gnomad4 SAS exome AF: 0.621

Gnomad4 FIN exome AF: 0.593

Gnomad4 NFE exome AF: 0.486

Gnomad4 OTH exome AF: 0.506

GnomAD4 genome AF: 0.520 AC: 79139 AN: 152172 Hom.: 20906 Cov.: 35 AF XY: 0.526 AC XY: 39180 AN XY: 74418

Gnomad4 AFR AF: 0.440

Gnomad4 AMR AF: 0.607

Gnomad4 ASJ AF: 0.543

Gnomad4 EAS AF: 0.717

Gnomad4 SAS AF: 0.639

Gnomad4 FIN AF: 0.590

Gnomad4 NFE AF: 0.516

Gnomad4 OTH AF: 0.476

Alfa AF: 0.511 Hom.: 19207

Bravo AF: 0.515

Asia WGS AF: 0.605 AC: 2105 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.6
DANN	Benign	0.50

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3755920; hg19: chr4-1243617;