rs10846670

Positions:

• chr12-124405685-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006312.6(NCOR2):​c.1483-3124G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 152,142 control chromosomes in the GnomAD database, including 17,696 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 0.47 (17696 hom., cov: 34)
• Consequence: NCOR2 NM_006312.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCOR2	NM_006312.6	c.1483-3124G>A		intron_variant		ENST00000405201.6	NP_006303.4
NCOR2	NM_001206654.2	c.1480-3124G>A		intron_variant			NP_001193583.1
NCOR2	NM_001077261.4	c.1480-3124G>A		intron_variant			NP_001070729.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCOR2	ENST00000405201.6	c.1483-3124G>A		intron_variant		1	NM_006312.6	ENSP00000384018.1
NCOR2	ENST00000429285.6	c.1480-3124G>A		intron_variant		1		ENSP00000400281.2
NCOR2	ENST00000404621.5	c.1480-3124G>A		intron_variant		1		ENSP00000384202.1
NCOR2	ENST00000458234.5	c.1483-3124G>A		intron_variant		1		ENSP00000402808.1

Frequencies

GnomAD3 genomes AF: 0.470 AC: 71507 AN: 152024 Hom.: 17686 Cov.: 34

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.679

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.619

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.503

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

GnomAD4 genome AF: 0.470 AC: 71544 AN: 152142 Hom.: 17696 Cov.: 34 AF XY: 0.468 AC XY: 34770 AN XY: 74364

Gnomad4 AFR AF: 0.365

Gnomad4 AMR AF: 0.485

Gnomad4 ASJ AF: 0.619

Gnomad4 EAS AF: 0.185

Gnomad4 SAS AF: 0.374

Gnomad4 FIN AF: 0.533

Gnomad4 NFE AF: 0.539

Gnomad4 OTH AF: 0.504

Alfa AF: 0.531 Hom.: 27055

Bravo AF: 0.464

Asia WGS AF: 0.311 AC: 1084 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.094
DANN	Benign	0.82

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

Publications

LitVar

Other links and lift over

dbSNP: rs10846670; hg19: chr12-124890231; COSMIC: COSV62295651;