rs6488932

Variant names:

• chr12-124517573-T-C
• rs6488932
• NM_006312.6:c.-118+17992A>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.-118+17992A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.048 in 152,240 control chromosomes in the GnomAD database, including 361 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 0.048 (361 hom., cov: 33)
• Consequence: NCOR2 NM_006312.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.108
• Publications: 2 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]

ENSG00000303311 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCOR2	NM_006312.6	c.-118+17992A>G		intron_variant	Intron 2 of 48	ENST00000405201.6	NP_006303.4
NCOR2	NM_001206654.2	c.-118+17992A>G		intron_variant	Intron 2 of 47		NP_001193583.1
NCOR2	NM_001077261.4	c.-118+17992A>G		intron_variant	Intron 2 of 47		NP_001070729.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCOR2	ENST00000405201.6	c.-118+17992A>G		intron_variant	Intron 2 of 48	1	NM_006312.6	ENSP00000384018.1

Frequencies

GnomAD3 genomes AF: 0.0480 AC: 7296 AN: 152122 Hom.: 361 Cov.: 33

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0355

Gnomad ASJ AF: 0.0386

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.00497

Gnomad FIN AF: 0.00894

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0168

Gnomad OTH AF: 0.0531

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

GnomAD4 genome AF: 0.0480 AC: 7312 AN: 152240 Hom.: 361 Cov.: 33 AF XY: 0.0474 AC XY: 3532 AN XY: 74440

African (AFR) AF: 0.125 AC: 5195 AN: 41530

American (AMR) AF: 0.0354 AC: 542 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0386 AC: 134 AN: 3472

East Asian (EAS) AF: 0.000388 AC: 2 AN: 5160

South Asian (SAS) AF: 0.00476 AC: 23 AN: 4828

European-Finnish (FIN) AF: 0.00894 AC: 95 AN: 10626

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0168 AC: 1143 AN: 67998

Other (OTH) AF: 0.0525 AC: 111 AN: 2114

Alfa AF: 0.0370 Hom.: 41

Bravo AF: 0.0538

Asia WGS AF: 0.0140 AC: 48 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.8
DANN	Benign	0.53
PhyloP100		0.11
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
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: rs6488932; hg19: chr12-125002119;