rs4962424

chr10-125041645-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000337195.10(CTBP2):c.-101-2490A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 151,840 control chromosomes in the GnomAD database, including 7,021 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 0.30 (7021 hom., cov: 29)
• Consequence: CTBP2 ENST00000337195.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.644

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTBP2	NM_001083914.3	c.-101-2490A>T		intron_variant
CTBP2	NM_001290214.3	c.-101-2490A>T		intron_variant
CTBP2	NM_001290215.3	c.-101-2490A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTBP2	ENST00000337195.10	c.-101-2490A>T		intron_variant		1		P1
CTBP2	ENST00000411419.7	c.-101-2490A>T		intron_variant		1		P1
CTBP2	ENST00000494626.6	c.-101-2490A>T		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45650 AN: 151720 Hom.: 7019 Cov.: 29

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.309

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.311

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.301 AC: 45684 AN: 151840 Hom.: 7021 Cov.: 29 AF XY: 0.300 AC XY: 22267 AN XY: 74180

Gnomad4 AFR AF: 0.265

Gnomad4 AMR AF: 0.336

Gnomad4 ASJ AF: 0.333

Gnomad4 EAS AF: 0.331

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.267

Gnomad4 NFE AF: 0.319

Gnomad4 OTH AF: 0.308

Alfa AF: 0.306 Hom.: 926

Bravo AF: 0.308

Asia WGS AF: 0.259 AC: 904 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.64
Dann	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs4962424; hg19: chr10-126730214;