rs1147289

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCOR2	NM_006312.6	c.233+921C>T		intron_variant		ENST00000405201.6	NP_006303.4
NCOR2	NM_001077261.4	c.233+921C>T		intron_variant			NP_001070729.2
NCOR2	NM_001206654.2	c.233+921C>T		intron_variant			NP_001193583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCOR2	ENST00000405201.6	c.233+921C>T		intron_variant		1	NM_006312.6	ENSP00000384018	P4

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

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.0689

Gnomad4 EAS AF: 0.179

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.0625

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.142

Alfa AF: 0.134 Hom.: 1896

Bravo AF: 0.137

Asia WGS AF: 0.127 AC: 440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.87

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

Publications

LitVar

Other links and lift over

dbSNP: rs1147289; hg19: chr12-124970066;