10-124989578-C-T

Variant names:

• chr10-124989578-C-T
• rs76963654
• NM_001329.4:c.1278G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_001329.4(CTBP2):​c.1278G>A​(p.Ala426Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000899 in 1,613,380 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000078 (0 hom.)
• Consequence: CTBP2 NM_001329.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0680
• Publications: 4 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=-0.43).
• BP6: Variant 10-124989578-C-T is Benign according to our data. Variant chr10-124989578-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 776551.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.068 with no splicing effect.
• BS2: High AC in GnomAd4 at 31 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001329.4. 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.1278G>A	p.Ala426Ala	synonymous	Exon 11 of 11	NP_001320.1	P56545-1
	CTBP2	NM_022802.3		c.2898G>A	p.Ala966Ala	synonymous	Exon 9 of 9	NP_073713.2	P56545-2
	CTBP2	NM_001363508.2		c.1482G>A	p.Ala494Ala	synonymous	Exon 9 of 9	NP_001350437.1	P56545-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTBP2	ENST00000337195.11	TSL:1 MANE Select	c.1278G>A	p.Ala426Ala	synonymous	Exon 11 of 11	ENSP00000338615.5	P56545-1
	CTBP2	ENST00000309035.11	TSL:1	c.2898G>A	p.Ala966Ala	synonymous	Exon 9 of 9	ENSP00000311825.6	P56545-2
	CTBP2	ENST00000334808.10	TSL:1	c.1482G>A	p.Ala494Ala	synonymous	Exon 9 of 9	ENSP00000357816.5	P56545-3

Frequencies

GnomAD3 genomes AF: 0.000204 AC: 31 AN: 152054 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0838 AC: 14706 AN: 175534 AF XY: 0.0851

Gnomad AFR exome AF: 0.132

Gnomad AMR exome AF: 0.0619

Gnomad ASJ exome AF: 0.0270

Gnomad EAS exome AF: 0.102

Gnomad FIN exome AF: 0.0613

Gnomad NFE exome AF: 0.103

Gnomad OTH exome AF: 0.0633

GnomAD4 exome AF: 0.0000780 AC: 114 AN: 1461208 Hom.: 0 Cov.: 31 AF XY: 0.0000894 AC XY: 65 AN XY: 726898

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.000224 AC: 10 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00224 AC: 89 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86206

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53264

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5598

European-Non Finnish (NFE) AF: 0.0000126 AC: 14 AN: 1111798

Other (OTH) AF: 0.0000166 AC: 1 AN: 60346

GnomAD4 genome AF: 0.000204 AC: 31 AN: 152172 Hom.: 0 Cov.: 31 AF XY: 0.000269 AC XY: 20 AN XY: 74406

African (AFR) AF: 0.00 AC: 0 AN: 41512

American (AMR) AF: 0.00176 AC: 27 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67988

Other (OTH) AF: 0.00 AC: 0 AN: 2106

Alfa AF: 0.0597 Hom.: 0

Bravo AF: 0.000159

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	4.2
DANN	Benign	0.84
PhyloP100		-0.068
Mutation Taster		=98/2	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: rs76963654; hg19: chr10-126678147; COSMIC: COSV58336138; COSMIC: COSV58336138;