12-124499070-T-C

Variant names:

• chr12-124499070-T-C
• rs1110904
• NM_006312.6:c.-117-3702A>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.-117-3702A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.8 in 152,268 control chromosomes in the GnomAD database, including 48,943 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 0.80 (48943 hom., cov: 33)
• Consequence: NCOR2 NM_006312.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.543
• Publications: 9 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 = 0.973 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.-117-3702A>G		intron	N/A	NP_006303.4	Q9Y618-1
	NCOR2	NM_001206654.2		c.-117-3702A>G		intron	N/A	NP_001193583.1	C9J0Q5
	NCOR2	NM_001077261.4		c.-117-3702A>G		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.-117-3702A>G		intron	N/A	ENSP00000384018.1	Q9Y618-1
	NCOR2	ENST00000429285.6	TSL:1	c.-117-3702A>G		intron	N/A	ENSP00000400281.2	C9J0Q5
	NCOR2	ENST00000404621.5	TSL:1	c.-117-3702A>G		intron	N/A	ENSP00000384202.1	C9JE98

Frequencies

GnomAD3 genomes AF: 0.800 AC: 121777 AN: 152152 Hom.: 48890 Cov.: 33

Gnomad AFR AF: 0.777

Gnomad AMI AF: 0.678

Gnomad AMR AF: 0.835

Gnomad ASJ AF: 0.756

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.869

Gnomad FIN AF: 0.850

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.783

Gnomad OTH AF: 0.798

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

GnomAD4 genome AF: 0.800 AC: 121890 AN: 152268 Hom.: 48943 Cov.: 33 AF XY: 0.807 AC XY: 60094 AN XY: 74468

African (AFR) AF: 0.778 AC: 32321 AN: 41548

American (AMR) AF: 0.835 AC: 12783 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.756 AC: 2623 AN: 3470

East Asian (EAS) AF: 0.995 AC: 5160 AN: 5184

South Asian (SAS) AF: 0.869 AC: 4195 AN: 4826

European-Finnish (FIN) AF: 0.850 AC: 9031 AN: 10624

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.783 AC: 53246 AN: 67996

Other (OTH) AF: 0.799 AC: 1690 AN: 2114

Alfa AF: 0.789 Hom.: 77322

Bravo AF: 0.798

Asia WGS AF: 0.925 AC: 3213 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	2.3
DANN	Benign	0.51
PhyloP100		-0.54
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1110904; hg19: chr12-124983616;