12-124341046-C-T

Variant names:

• chr12-124341046-C-T
• rs1794973
• NM_006312.6:c.5189-295G>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.5189-295G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 152,134 control chromosomes in the GnomAD database, including 17,836 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 0.43 (17836 hom., cov: 32)
• Consequence: NCOR2 NM_006312.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.20
• Publications: 8 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.586 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.5189-295G>A		intron	N/A	NP_006303.4	Q9Y618-1
	NCOR2	NM_001206654.2		c.5159-295G>A		intron	N/A	NP_001193583.1	C9J0Q5
	NCOR2	NM_001077261.4		c.5159-295G>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.5189-295G>A		intron	N/A	ENSP00000384018.1	Q9Y618-1
	NCOR2	ENST00000429285.6	TSL:1	c.5159-295G>A		intron	N/A	ENSP00000400281.2	C9J0Q5
	NCOR2	ENST00000404621.5	TSL:1	c.5159-295G>A		intron	N/A	ENSP00000384202.1	C9JE98

Frequencies

GnomAD3 genomes AF: 0.434 AC: 66027 AN: 152016 Hom.: 17835 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.556

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.636

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.531

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.483

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

GnomAD4 genome AF: 0.434 AC: 66035 AN: 152134 Hom.: 17836 Cov.: 32 AF XY: 0.431 AC XY: 32050 AN XY: 74364

African (AFR) AF: 0.108 AC: 4478 AN: 41554

American (AMR) AF: 0.545 AC: 8337 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.636 AC: 2209 AN: 3472

East Asian (EAS) AF: 0.360 AC: 1857 AN: 5162

South Asian (SAS) AF: 0.360 AC: 1733 AN: 4818

European-Finnish (FIN) AF: 0.531 AC: 5613 AN: 10562

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.590 AC: 40131 AN: 67962

Other (OTH) AF: 0.485 AC: 1025 AN: 2112

Alfa AF: 0.530 Hom.: 52406

Bravo AF: 0.425

Asia WGS AF: 0.351 AC: 1223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.12
DANN	Benign	0.69
PhyloP100		-3.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1794973; hg19: chr12-124825592;