chr4-1249829-T-C

Variant names:

• chr4-1249829-T-C
• rs3755920
• NM_001377190.1:c.-369A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 20 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-DT (HGNC:28307): (CTBP1 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377190.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTBP1	NM_001377190.1		c.-369A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 10	NP_001364119.1
	CTBP1	NM_001377193.1		c.-369A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 10	NP_001364122.1
	CTBP1	NM_001377190.1		c.-369A>G		5_prime_UTR	Exon 1 of 10	NP_001364119.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTBP1	ENST00000506180.5	TSL:5	c.-198A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	ENSP00000424684.2
	CTBP1	ENST00000515399.5	TSL:3	c.-369A>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	ENSP00000425053.1
	CTBP1	ENST00000506180.5	TSL:5	c.-198A>G		5_prime_UTR	Exon 1 of 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

African (AFR) AF: 0.388 AC: 146 AN: 376

American (AMR) AF: 0.675 AC: 493 AN: 730

Ashkenazi Jewish (ASJ) AF: 0.522 AC: 509 AN: 976

East Asian (EAS) AF: 0.636 AC: 140 AN: 220

South Asian (SAS) AF: 0.621 AC: 12085 AN: 19468

European-Finnish (FIN) AF: 0.593 AC: 1668 AN: 2814

Middle Eastern (MID) AF: 0.382 AC: 532 AN: 1392

European-Non Finnish (NFE) AF: 0.486 AC: 13470 AN: 27742

Other (OTH) AF: 0.506 AC: 1045 AN: 2064

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

African (AFR) AF: 0.440 AC: 18256 AN: 41530

American (AMR) AF: 0.607 AC: 9288 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.543 AC: 1885 AN: 3470

East Asian (EAS) AF: 0.717 AC: 3715 AN: 5178

South Asian (SAS) AF: 0.639 AC: 3088 AN: 4832

European-Finnish (FIN) AF: 0.590 AC: 6256 AN: 10598

Middle Eastern (MID) AF: 0.418 AC: 122 AN: 292

European-Non Finnish (NFE) AF: 0.516 AC: 35047 AN: 67958

Other (OTH) AF: 0.476 AC: 1007 AN: 2114

Alfa AF: 0.507 Hom.: 26112

Bravo AF: 0.515

Asia WGS AF: 0.605 AC: 2105 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.6
DANN	Benign	0.50
PhyloP100		-0.96
PromoterAI		0.015	Neutral

Splicing

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

Other links and lift over

dbSNP: rs3755920; hg19: chr4-1243617;