rs1794942

Variant names:

• chr12-124472607-C-T
• rs1794942
• NM_006312.6:c.591+345G>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.591+345G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 152,200 control chromosomes in the GnomAD database, including 1,858 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 0.15 (1858 hom., cov: 33)
• Consequence: NCOR2 NM_006312.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42
• Publications: 6 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCOR2	NM_006312.6	c.591+345G>A		intron_variant	Intron 6 of 48	ENST00000405201.6	NP_006303.4
NCOR2	NM_001206654.2	c.591+345G>A		intron_variant	Intron 6 of 47		NP_001193583.1
NCOR2	NM_001077261.4	c.591+345G>A		intron_variant	Intron 6 of 47		NP_001070729.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCOR2	ENST00000405201.6	c.591+345G>A		intron_variant	Intron 6 of 48	1	NM_006312.6	ENSP00000384018.1

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22879 AN: 152082 Hom.: 1849 Cov.: 33

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.0529

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.158

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

GnomAD4 genome AF: 0.150 AC: 22903 AN: 152200 Hom.: 1858 Cov.: 33 AF XY: 0.147 AC XY: 10928 AN XY: 74424

African (AFR) AF: 0.202 AC: 8387 AN: 41504

American (AMR) AF: 0.180 AC: 2759 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 574 AN: 3472

East Asian (EAS) AF: 0.213 AC: 1104 AN: 5182

South Asian (SAS) AF: 0.157 AC: 759 AN: 4822

European-Finnish (FIN) AF: 0.0529 AC: 562 AN: 10618

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8227 AN: 67996

Other (OTH) AF: 0.156 AC: 329 AN: 2110

Alfa AF: 0.137 Hom.: 3421

Bravo AF: 0.166

Asia WGS AF: 0.167 AC: 582 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.0
DANN	Benign	0.57
PhyloP100		1.4
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: rs1794942; hg19: chr12-124957153;