rs1147289

Variant names:

• chr12-124485520-G-A
• rs1147289
• NM_006312.6:c.233+921C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-124485520-G-A
• chr12-124485520-G-T

Variant summary

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

The NM_006312.6(NCOR2):​c.233+921C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,278 control chromosomes in the GnomAD database, including 1,289 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 (1289 hom., cov: 33)
• Consequence: NCOR2 NM_006312.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.311
• Publications: 8 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006312.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCOR2	NM_006312.6	MANE Select	c.233+921C>T		intron	N/A	NP_006303.4
	NCOR2	NM_001206654.2		c.233+921C>T		intron	N/A	NP_001193583.1
	NCOR2	NM_001077261.4		c.233+921C>T		intron	N/A	NP_001070729.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCOR2	ENST00000405201.6	TSL:1 MANE Select	c.233+921C>T		intron	N/A	ENSP00000384018.1
	NCOR2	ENST00000429285.6	TSL:1	c.233+921C>T		intron	N/A	ENSP00000400281.2
	NCOR2	ENST00000404621.5	TSL:1	c.233+921C>T		intron	N/A	ENSP00000384202.1

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19600 AN: 152160 Hom.: 1282 Cov.: 33

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.0689

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.0625

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.144

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

GnomAD4 genome AF: 0.129 AC: 19616 AN: 152278 Hom.: 1289 Cov.: 33 AF XY: 0.125 AC XY: 9322 AN XY: 74462

African (AFR) AF: 0.124 AC: 5155 AN: 41540

American (AMR) AF: 0.163 AC: 2488 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0689 AC: 239 AN: 3468

East Asian (EAS) AF: 0.179 AC: 925 AN: 5164

South Asian (SAS) AF: 0.119 AC: 575 AN: 4832

European-Finnish (FIN) AF: 0.0625 AC: 664 AN: 10626

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9117 AN: 68024

Other (OTH) AF: 0.142 AC: 301 AN: 2114

Alfa AF: 0.134 Hom.: 2418

Bravo AF: 0.137

Asia WGS AF: 0.127 AC: 440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.87
PhyloP100		-0.31
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: rs1147289; hg19: chr12-124970066;