rs10846670

Variant names:

• chr12-124405685-C-T
• rs10846670
• NM_006312.6:c.1483-3124G>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.1483-3124G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 152,142 control chromosomes in the GnomAD database, including 17,696 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 0.47 (17696 hom., cov: 34)
• Consequence: NCOR2 NM_006312.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72
• Publications: 5 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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.534 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCOR2	NM_006312.6	MANE Select	c.1483-3124G>A		intron	N/A	NP_006303.4	Q9Y618-1
	NCOR2	NM_001206654.2		c.1480-3124G>A		intron	N/A	NP_001193583.1	C9J0Q5
	NCOR2	NM_001077261.4		c.1480-3124G>A		intron	N/A	NP_001070729.2	C9JE98

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCOR2	ENST00000405201.6	TSL:1 MANE Select	c.1483-3124G>A		intron	N/A	ENSP00000384018.1	Q9Y618-1
	NCOR2	ENST00000429285.6	TSL:1	c.1480-3124G>A		intron	N/A	ENSP00000400281.2	C9J0Q5
	NCOR2	ENST00000404621.5	TSL:1	c.1480-3124G>A		intron	N/A	ENSP00000384202.1	C9JE98

Frequencies

GnomAD3 genomes AF: 0.470 AC: 71507 AN: 152024 Hom.: 17686 Cov.: 34

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.679

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.619

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.503

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

GnomAD4 genome AF: 0.470 AC: 71544 AN: 152142 Hom.: 17696 Cov.: 34 AF XY: 0.468 AC XY: 34770 AN XY: 74364

African (AFR) AF: 0.365 AC: 15131 AN: 41506

American (AMR) AF: 0.485 AC: 7412 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.619 AC: 2149 AN: 3472

East Asian (EAS) AF: 0.185 AC: 955 AN: 5174

South Asian (SAS) AF: 0.374 AC: 1803 AN: 4824

European-Finnish (FIN) AF: 0.533 AC: 5642 AN: 10582

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.539 AC: 36618 AN: 67978

Other (OTH) AF: 0.504 AC: 1063 AN: 2108

Alfa AF: 0.525 Hom.: 33158

Bravo AF: 0.464

Asia WGS AF: 0.311 AC: 1084 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.094
DANN	Benign	0.82
PhyloP100		-1.7
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: rs10846670; hg19: chr12-124890231; COSMIC: COSV62295651;