ENST00000334808.10:c.-10C>T

Variant names:

• chr10-125005818-G-A
• rs377616232
• ENST00000334808.10:c.-10C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The ENST00000334808.10(CTBP2):​c.-10C>T 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 0.000923 in 1,608,456 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00050 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00097 (1 hom.)
• Consequence: CTBP2 ENST00000334808.10 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.646
• Publications: 0 publications found

Genes affected

CTBP2 (HGNC:2495): (C-terminal binding protein 2) This gene produces alternative transcripts encoding two distinct proteins. One protein is a transcriptional repressor, while the other isoform is a major component of specialized synapses known as synaptic ribbons. Both proteins contain a NAD+ binding domain similar to NAD+-dependent 2-hydroxyacid dehydrogenases. A portion of the 3' untranslated region was used to map this gene to chromosome 21q21.3; however, it was noted that similar loci elsewhere in the genome are likely. Blast analysis shows that this gene is present on chromosome 10. Several transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Feb 2014]

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 10-125005818-G-A is Benign according to our data. Variant chr10-125005818-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3051217.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd4 at 76 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000334808.10. 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
	CTBP2	NM_001329.4	MANE Select	c.59-2326C>T		intron	N/A	NP_001320.1	P56545-1
	CTBP2	NM_001363508.2		c.-10C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	NP_001350437.1	P56545-3
	CTBP2	NM_001363508.2		c.-10C>T		5_prime_UTR	Exon 1 of 9	NP_001350437.1	P56545-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTBP2	ENST00000334808.10	TSL:1	c.-10C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	ENSP00000357816.5	P56545-3
	CTBP2	ENST00000334808.10	TSL:1	c.-10C>T		5_prime_UTR	Exon 1 of 9	ENSP00000357816.5	P56545-3
	CTBP2	ENST00000337195.11	TSL:1 MANE Select	c.59-2326C>T		intron	N/A	ENSP00000338615.5	P56545-1

Frequencies

GnomAD3 genomes AF: 0.000499 AC: 76 AN: 152212 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000911

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000540 AC: 129 AN: 239034 AF XY: 0.000564

Gnomad AFR exome AF: 0.000211

Gnomad AMR exome AF: 0.0000587

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000141

Gnomad NFE exome AF: 0.000830

Gnomad OTH exome AF: 0.000169

GnomAD4 exome AF: 0.000968 AC: 1409 AN: 1456126 Hom.: 1 Cov.: 31 AF XY: 0.000946 AC XY: 685 AN XY: 723774

African (AFR) AF: 0.000150 AC: 5 AN: 33300

American (AMR) AF: 0.0000900 AC: 4 AN: 44450

Ashkenazi Jewish (ASJ) AF: 0.0000771 AC: 2 AN: 25928

East Asian (EAS) AF: 0.00 AC: 0 AN: 39634

South Asian (SAS) AF: 0.00151 AC: 130 AN: 85986

European-Finnish (FIN) AF: 0.0000192 AC: 1 AN: 52078

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00109 AC: 1214 AN: 1108848

Other (OTH) AF: 0.000881 AC: 53 AN: 60146

GnomAD4 genome AF: 0.000499 AC: 76 AN: 152330 Hom.: 0 Cov.: 32 AF XY: 0.000456 AC XY: 34 AN XY: 74486

African (AFR) AF: 0.000168 AC: 7 AN: 41568

American (AMR) AF: 0.000131 AC: 2 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.000911 AC: 62 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000553 Hom.: 0

Bravo AF: 0.000529

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	CTBP2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.44
DANN	Benign	0.61
PhyloP100		-0.65
PromoterAI		0.019	Neutral
Mutation Taster		=100/0	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: rs377616232; hg19: chr10-126694387;