rs6488932

Positions:

• chr12-124517573-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

NCOR2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
NCOR2	NM_006312.6	c.-118+17992A>G		intron_variant		ENST00000405201.6	NP_006303.4
NCOR2	NM_001206654.2	c.-118+17992A>G		intron_variant			NP_001193583.1
NCOR2	NM_001077261.4	c.-118+17992A>G		intron_variant			NP_001070729.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCOR2	ENST00000405201.6	c.-118+17992A>G		intron_variant		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

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.0354

Gnomad4 ASJ AF: 0.0386

Gnomad4 EAS AF: 0.000388

Gnomad4 SAS AF: 0.00476

Gnomad4 FIN AF: 0.00894

Gnomad4 NFE AF: 0.0168

Gnomad4 OTH AF: 0.0525

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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6488932; hg19: chr12-125002119;