rs4962416

Variant names:

Variant summary

Our verdict is The variant received -12 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_Strong

The NM_001329.4(CTBP2):c.59-4811A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.228 (AC=34,731) in the gnomAD database across 152,154 control chromosomes, including 4,414 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.303. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.23 ( 4414 hom., cov: 33)

Consequence

CTBP2
NM_001329.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.08

Publications

126 publications found

Variant links:

COSMIC-nc: COSV58332887

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]

CTBP2 links:

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new If you want to explore the variant's impact on the transcript NM_001329.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

Our verdict: Benign. The variant received -12 points.

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).

BA1

GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.3032 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_001329.4. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CTBP2	NM_001329.4	MANE Select	c.59-4811A>G	intron	N/A	NP_001320.1	P56545-1
CTBP2	NM_022802.3		c.1679-4811A>G	intron	N/A	NP_073713.2	P56545-2
CTBP2	NM_001083914.3		c.59-4811A>G	intron	N/A	NP_001077383.1	P56545-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CTBP2	ENST00000337195.11	TSL:1 MANE Select	c.59-4811A>G	intron	N/A	ENSP00000338615.5	P56545-1
CTBP2	ENST00000309035.11	TSL:1	c.1679-4811A>G	intron	N/A	ENSP00000311825.6	P56545-2
CTBP2	ENST00000411419.7	TSL:1	c.59-4811A>G	intron	N/A	ENSP00000410474.2	P56545-1

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 4 sources Large-scale international reference populations
GnomAD3 genomes	0.228	34723	4415	152038	33
GnomAD4 genome	0.228	34731	4414	152154	33
TOPMed (Bravo)	0.229	60692	7612	264690
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	0.264	180597	24881	684402
Local & regional cohorts 10 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	0.243	569	77	2342
ChinaMAP Phase 1	0.0113
Denmark Genome	0.230	69		300
GenomeAsia100K	0.128	445		3478
Korea4K (4,157 Koreans)	0.00968	70		7234
Qatari Genome	0.313	55		176
ToMMo 61KJPN (+60KJPN MNV)	0.00918	1126	8	122660
Turkish Variome	0.325	503	95	1546
UK10K	0.284	2151		7562
WBBC (Westlake BioBank for Chinese) pilot	0.00614	55	0	8960

Showing 14 sources

Tested, but no data found:GnomAD4 exomeIf GnomAD4 is missing, the position is probably not covered by the project.

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated prediction	Prediction	Score
AlphaGenome AVI	Benign	-	2.5
BayesDel_noAF	Benign	-	-1.0
CADD	Benign	-	2.1
DANN	Benign	-	0.81
GPN-Star LLR	N/A	-	5.7
GPN-Star score	N/A	-	1.9
Mutation Taster	N/A	polymorphism (auto)	100/0
PhyloP100	Benign	-	-1.1

Showing 8 of 8 scores

Splicing Scores

Algorithm	Calibrated prediction	Prediction	Score
Pangolin (max)	Benign	-	0.0
SpliceAI score (max)	Benign	- Details are displayed if max score is > 0.2	0.0

Showing 2 of 2 scores

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational Scores

Splicing Scores

Publications

Other links and lift over