chr10-124993314-C-T

Variant names:

• chr10-124993314-C-T
• rs76804352
• NM_001329.4:c.927G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001329.4(CTBP2):​c.927G>A​(p.Pro309Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00326 in 1,608,626 control chromosomes in the GnomAD database, including 122 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (68 hom., cov: 33)
  • Exomes 𝑓: 0.0018 (54 hom.)
• Consequence: CTBP2 NM_001329.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -6.20
• Publications: 3 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 10-124993314-C-T is Benign according to our data. Variant chr10-124993314-C-T is described in ClinVar as Benign. ClinVar VariationId is 779348.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-6.2 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0569 is higher than 0.05.

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.927G>A	p.Pro309Pro	synonymous	Exon 9 of 11	NP_001320.1	P56545-1
	CTBP2	NM_022802.3		c.2547G>A	p.Pro849Pro	synonymous	Exon 7 of 9	NP_073713.2	P56545-2
	CTBP2	NM_001363508.2		c.1131G>A	p.Pro377Pro	synonymous	Exon 7 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.927G>A	p.Pro309Pro	synonymous	Exon 9 of 11	ENSP00000338615.5	P56545-1
	CTBP2	ENST00000309035.11	TSL:1	c.2547G>A	p.Pro849Pro	synonymous	Exon 7 of 9	ENSP00000311825.6	P56545-2
	CTBP2	ENST00000334808.10	TSL:1	c.1131G>A	p.Pro377Pro	synonymous	Exon 7 of 9	ENSP00000357816.5	P56545-3

Frequencies

GnomAD3 genomes AF: 0.0171 AC: 2601 AN: 152114 Hom.: 67 Cov.: 33

Gnomad AFR AF: 0.0587

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00759

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.0139

GnomAD2 exomes AF: 0.00456 AC: 1145 AN: 250838 AF XY: 0.00352

Gnomad AFR exome AF: 0.0602

Gnomad AMR exome AF: 0.00362

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000203

Gnomad OTH exome AF: 0.00180

GnomAD4 exome AF: 0.00181 AC: 2633 AN: 1456394 Hom.: 54 Cov.: 32 AF XY: 0.00163 AC XY: 1181 AN XY: 723530

African (AFR) AF: 0.0565 AC: 1887 AN: 33380

American (AMR) AF: 0.00464 AC: 207 AN: 44650

Ashkenazi Jewish (ASJ) AF: 0.000115 AC: 3 AN: 26064

East Asian (EAS) AF: 0.00 AC: 0 AN: 39548

South Asian (SAS) AF: 0.000151 AC: 13 AN: 86002

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53312

Middle Eastern (MID) AF: 0.00209 AC: 12 AN: 5740

European-Non Finnish (NFE) AF: 0.000245 AC: 271 AN: 1107614

Other (OTH) AF: 0.00399 AC: 240 AN: 60084

GnomAD4 genome AF: 0.0172 AC: 2614 AN: 152232 Hom.: 68 Cov.: 33 AF XY: 0.0163 AC XY: 1216 AN XY: 74416

African (AFR) AF: 0.0589 AC: 2444 AN: 41516

American (AMR) AF: 0.00758 AC: 116 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.000289 AC: 1 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000323 AC: 22 AN: 68028

Other (OTH) AF: 0.0137 AC: 29 AN: 2112

Alfa AF: 0.00815 Hom.: 15

Bravo AF: 0.0200

Asia WGS AF: 0.00520 AC: 18 AN: 3478

EpiCase AF: 0.000383

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	3.7
DANN	Benign	0.92
PhyloP100		-6.2
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: rs76804352; hg19: chr10-126681883;