12-124472006-C-T

Variant names:

• chr12-124472006-C-T
• rs1243733
• NM_006312.6:c.591+946G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006312.6(NCOR2):​c.591+946G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,220 control chromosomes in the GnomAD database, including 1,380 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 0.13 (1380 hom., cov: 33)
• Consequence: NCOR2 NM_006312.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.127
• Publications: 4 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCOR2	NM_006312.6	c.591+946G>A		intron_variant	Intron 6 of 48	ENST00000405201.6	NP_006303.4
NCOR2	NM_001206654.2	c.591+946G>A		intron_variant	Intron 6 of 47		NP_001193583.1
NCOR2	NM_001077261.4	c.591+946G>A		intron_variant	Intron 6 of 47		NP_001070729.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCOR2	ENST00000405201.6	c.591+946G>A		intron_variant	Intron 6 of 48	1	NM_006312.6	ENSP00000384018.1

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19236 AN: 152100 Hom.: 1371 Cov.: 33

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.0539

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.0451

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0953

Gnomad OTH AF: 0.130

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

GnomAD4 genome AF: 0.127 AC: 19257 AN: 152220 Hom.: 1380 Cov.: 33 AF XY: 0.123 AC XY: 9181 AN XY: 74436

African (AFR) AF: 0.188 AC: 7812 AN: 41498

American (AMR) AF: 0.144 AC: 2208 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0539 AC: 187 AN: 3472

East Asian (EAS) AF: 0.214 AC: 1107 AN: 5176

South Asian (SAS) AF: 0.125 AC: 603 AN: 4828

European-Finnish (FIN) AF: 0.0451 AC: 478 AN: 10610

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0953 AC: 6480 AN: 68022

Other (OTH) AF: 0.127 AC: 269 AN: 2112

Alfa AF: 0.110 Hom.: 1608

Bravo AF: 0.139

Asia WGS AF: 0.148 AC: 515 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.9
DANN	Benign	0.50
PhyloP100		-0.13
Mutation Taster		=100/0	polymorphism (auto)

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: rs1243733; hg19: chr12-124956552;