12-124399807-A-G

Variant names:

• chr12-124399807-A-G
• rs10846666
• NM_006312.6:c.1813+694T>C

Variant summary

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

The NM_006312.6(NCOR2):​c.1813+694T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 152,076 control chromosomes in the GnomAD database, including 2,755 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 0.17 (2755 hom., cov: 32)
• Consequence: NCOR2 NM_006312.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47
• Publications: 4 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.488 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.1813+694T>C		intron	N/A	NP_006303.4
	NCOR2	NM_001206654.2		c.1810+694T>C		intron	N/A	NP_001193583.1
	NCOR2	NM_001077261.4		c.1810+694T>C		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.1813+694T>C		intron	N/A	ENSP00000384018.1
	NCOR2	ENST00000429285.6	TSL:1	c.1810+694T>C		intron	N/A	ENSP00000400281.2
	NCOR2	ENST00000404621.5	TSL:1	c.1810+694T>C		intron	N/A	ENSP00000384202.1

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25786 AN: 151958 Hom.: 2750 Cov.: 32

Gnomad AFR AF: 0.0843

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.504

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.170 AC: 25797 AN: 152076 Hom.: 2755 Cov.: 32 AF XY: 0.175 AC XY: 13027 AN XY: 74356

African (AFR) AF: 0.0845 AC: 3507 AN: 41506

American (AMR) AF: 0.205 AC: 3138 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 442 AN: 3464

East Asian (EAS) AF: 0.504 AC: 2595 AN: 5150

South Asian (SAS) AF: 0.275 AC: 1324 AN: 4816

European-Finnish (FIN) AF: 0.190 AC: 2004 AN: 10570

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.181 AC: 12288 AN: 67962

Other (OTH) AF: 0.162 AC: 341 AN: 2110

Alfa AF: 0.173 Hom.: 4246

Bravo AF: 0.167

Asia WGS AF: 0.348 AC: 1210 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.24
DANN	Benign	0.62
PhyloP100		-1.5
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: rs10846666; hg19: chr12-124884353;