rs12582168

Variant names:

• chr12-124409638-T-C
• rs12582168
• NM_006312.6:c.1483-7077A>G

Your query was ambiguous. Multiple possible variants found:

• chr12-124409638-T-C
• chr12-124409638-T-G

Variant summary

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

The NM_006312.6(NCOR2):​c.1483-7077A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 151,774 control chromosomes in the GnomAD database, including 4,136 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 0.23 (4136 hom., cov: 31)
• Consequence: NCOR2 NM_006312.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.366
• Publications: 10 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCOR2	NM_006312.6	c.1483-7077A>G		intron_variant	Intron 15 of 48	ENST00000405201.6	NP_006303.4
NCOR2	NM_001206654.2	c.1480-7077A>G		intron_variant	Intron 15 of 47		NP_001193583.1
NCOR2	NM_001077261.4	c.1480-7077A>G		intron_variant	Intron 15 of 47		NP_001070729.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCOR2	ENST00000405201.6	c.1483-7077A>G		intron_variant	Intron 15 of 48	1	NM_006312.6	ENSP00000384018.1
NCOR2	ENST00000429285.6	c.1480-7077A>G		intron_variant	Intron 14 of 46	1		ENSP00000400281.2
NCOR2	ENST00000404621.5	c.1480-7077A>G		intron_variant	Intron 14 of 46	1		ENSP00000384202.1
NCOR2	ENST00000458234.5	c.1483-7077A>G		intron_variant	Intron 15 of 32	1		ENSP00000402808.1

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34607 AN: 151654 Hom.: 4116 Cov.: 31

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.236

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

GnomAD4 genome AF: 0.228 AC: 34669 AN: 151774 Hom.: 4136 Cov.: 31 AF XY: 0.226 AC XY: 16737 AN XY: 74150

African (AFR) AF: 0.249 AC: 10307 AN: 41362

American (AMR) AF: 0.286 AC: 4361 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 780 AN: 3462

East Asian (EAS) AF: 0.284 AC: 1456 AN: 5130

South Asian (SAS) AF: 0.258 AC: 1239 AN: 4794

European-Finnish (FIN) AF: 0.138 AC: 1461 AN: 10590

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.210 AC: 14271 AN: 67894

Other (OTH) AF: 0.243 AC: 510 AN: 2102

Alfa AF: 0.217 Hom.: 9906

Bravo AF: 0.240

Asia WGS AF: 0.274 AC: 950 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.0
DANN	Benign	0.58
PhyloP100		0.37
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: rs12582168; hg19: chr12-124894184;