4-1249829-T-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001377190.1(CTBP1):​c.-369A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 35)
• Consequence: CTBP1 NM_001377190.1 5_prime_UTR
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTBP1	NM_001377190.1		c.-369A>C		5_prime_UTR	Exon 1 of 10	NP_001364119.1	H0Y8U5
	CTBP1	NM_001377193.1		c.-369A>C		5_prime_UTR	Exon 1 of 10	NP_001364122.1	Q13363-2
	CTBP1	NM_001377189.1		c.-189+331A>C		intron	N/A	NP_001364118.1	H0Y8U5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTBP1	ENST00000506180.5	TSL:5	c.-198A>C		5_prime_UTR	Exon 1 of 5	ENSP00000424684.2	D6RAX2
	CTBP1	ENST00000515399.5	TSL:3	c.-369A>C		5_prime_UTR	Exon 1 of 5	ENSP00000425053.1	E7ESU7
	CTBP1	ENST00000503594.6	TSL:2	c.-189+331A>C		intron	N/A	ENSP00000422148.2	H0Y8U5

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.2
DANN	Benign	0.40
PhyloP100		-0.96
PromoterAI		0.025	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;