NM_006312.6:c.-164-13776C>T

Variant names:

• chr12-124549387-G-A
• rs12423712
• NM_006312.6:c.-164-13776C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B.

Score: -12 - Benign

-12

BP4_StrongBA1

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
• Publications: 12 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=-0.83).
• 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 rank	MANE	Protein	UniProt
NCOR2	NM_006312.6	c.-164-13776C>T		intron_variant	Intron 1 of 48	ENST00000405201.6	NP_006303.4
NCOR2	NM_001206654.2	c.-164-13776C>T		intron_variant	Intron 1 of 47		NP_001193583.1
NCOR2	NM_001077261.4	c.-164-13776C>T		intron_variant	Intron 1 of 47		NP_001070729.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCOR2	ENST00000405201.6	c.-164-13776C>T		intron_variant	Intron 1 of 48	1	NM_006312.6	ENSP00000384018.1
NCOR2	ENST00000458234.5	c.-164-13776C>T		intron_variant	Intron 1 of 32	1		ENSP00000402808.1
NCOR2	ENST00000542565.1	n.283-13776C>T		intron_variant	Intron 1 of 3	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

African (AFR) AF: 0.106 AC: 4384 AN: 41520

American (AMR) AF: 0.0946 AC: 1447 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0516 AC: 179 AN: 3470

East Asian (EAS) AF: 0.0189 AC: 98 AN: 5178

South Asian (SAS) AF: 0.0741 AC: 358 AN: 4830

European-Finnish (FIN) AF: 0.0550 AC: 583 AN: 10604

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0689 AC: 4683 AN: 67986

Other (OTH) AF: 0.0639 AC: 135 AN: 2114

Alfa AF: 0.0722 Hom.: 1407

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
PhyloP100		-0.55

Splicing

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

Other links and lift over

dbSNP: rs12423712; hg19: chr12-125033933;