rs12423712

Positions:

• chr12-124549387-G-A

Variant summary

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

The NM_006312.6(NCOR2):​c.-164-13776C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0781 in 152,200 control chromosomes in the GnomAD database, including 512 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 0.078 (512 hom., cov: 32)
• Consequence: NCOR2 NM_006312.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.548

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCOR2	NM_006312.6	c.-164-13776C>T		intron_variant		ENST00000405201.6
NCOR2	NM_001077261.4	c.-164-13776C>T		intron_variant
NCOR2	NM_001206654.2	c.-164-13776C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCOR2	ENST00000405201.6	c.-164-13776C>T		intron_variant		1	NM_006312.6	P4
NCOR2	ENST00000458234.5	c.-164-13776C>T		intron_variant		1
NCOR2	ENST00000542565.1	n.283-13776C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0782 AC: 11889 AN: 152082 Hom.: 511 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0947

Gnomad ASJ AF: 0.0516

Gnomad EAS AF: 0.0191

Gnomad SAS AF: 0.0739

Gnomad FIN AF: 0.0550

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0689

Gnomad OTH AF: 0.0645

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

GnomAD4 genome AF: 0.0781 AC: 11888 AN: 152200 Hom.: 512 Cov.: 32 AF XY: 0.0781 AC XY: 5811 AN XY: 74416

Gnomad4 AFR AF: 0.106

Gnomad4 AMR AF: 0.0946

Gnomad4 ASJ AF: 0.0516

Gnomad4 EAS AF: 0.0189

Gnomad4 SAS AF: 0.0741

Gnomad4 FIN AF: 0.0550

Gnomad4 NFE AF: 0.0689

Gnomad4 OTH AF: 0.0639

Alfa AF: 0.0702 Hom.: 594

Bravo AF: 0.0812

Asia WGS AF: 0.0530 AC: 184 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.57
DANN	Benign	0.81

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12423712; hg19: chr12-125033933;