chr12-124518506-C-T

Position:

• chr12-124518506-C-T

Variant summary

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

The NM_006312.6(NCOR2):​c.-118+17059G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00959 in 152,384 control chromosomes in the GnomAD database, including 60 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 0.0096 (60 hom., cov: 33)
• Consequence: NCOR2 NM_006312.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.20

Genes affected

NCOR2 (HGNC:7673): (nuclear receptor corepressor 2) This gene encodes a nuclear receptor co-repressor that mediates transcriptional silencing of certain target genes. The encoded protein is a member of a family of thyroid hormone- and retinoic acid receptor-associated co-repressors. This protein acts as part of a multisubunit complex which includes histone deacetylases to modify chromatin structure that prevents basal transcriptional activity of target genes. Aberrant expression of this gene is associated with certain cancers. Alternate splicing results in multiple transcript variants encoding different isoforms.[provided by RefSeq, Apr 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCOR2	NM_006312.6	c.-118+17059G>A		intron_variant		ENST00000405201.6	NP_006303.4
NCOR2	NM_001077261.4	c.-118+17059G>A		intron_variant			NP_001070729.2
NCOR2	NM_001206654.2	c.-118+17059G>A		intron_variant			NP_001193583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCOR2	ENST00000405201.6	c.-118+17059G>A		intron_variant		1	NM_006312.6	ENSP00000384018	P4

Frequencies

GnomAD3 genomes AF: 0.00953 AC: 1451 AN: 152266 Hom.: 58 Cov.: 33

Gnomad AFR AF: 0.00174

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0753

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.0133

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00162

Gnomad OTH AF: 0.0148

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

GnomAD4 genome AF: 0.00959 AC: 1461 AN: 152384 Hom.: 60 Cov.: 33 AF XY: 0.0114 AC XY: 853 AN XY: 74514

Gnomad4 AFR AF: 0.00173

Gnomad4 AMR AF: 0.0760

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.0131

Gnomad4 SAS AF: 0.00186

Gnomad4 FIN AF: 0.000659

Gnomad4 NFE AF: 0.00162

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.00455 Hom.: 0

Bravo AF: 0.0149

Asia WGS AF: 0.00577 AC: 20 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	13
DANN	Benign	0.92

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12426064; hg19: chr12-125003052;