rs12321007

Variant names:

• chr12-124398555-G-A
• rs12321007
• NM_006312.6:c.1814-374C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006312.6(NCOR2):​c.1814-374C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 152,206 control chromosomes in the GnomAD database, including 6,544 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 0.27 (6544 hom., cov: 33)
• Consequence: NCOR2 NM_006312.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.07
• Publications: 3 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCOR2	NM_006312.6	c.1814-374C>T		intron_variant	Intron 17 of 48	ENST00000405201.6	NP_006303.4
NCOR2	NM_001206654.2	c.1811-374C>T		intron_variant	Intron 17 of 47		NP_001193583.1
NCOR2	NM_001077261.4	c.1811-374C>T		intron_variant	Intron 17 of 47		NP_001070729.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCOR2	ENST00000405201.6	c.1814-374C>T		intron_variant	Intron 17 of 48	1	NM_006312.6	ENSP00000384018.1
NCOR2	ENST00000429285.6	c.1811-374C>T		intron_variant	Intron 16 of 46	1		ENSP00000400281.2
NCOR2	ENST00000404621.5	c.1811-374C>T		intron_variant	Intron 16 of 46	1		ENSP00000384202.1
NCOR2	ENST00000458234.5	c.1814-374C>T		intron_variant	Intron 17 of 32	1		ENSP00000402808.1

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40332 AN: 152088 Hom.: 6538 Cov.: 33

Gnomad AFR AF: 0.0838

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.310

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

GnomAD4 genome AF: 0.265 AC: 40344 AN: 152206 Hom.: 6544 Cov.: 33 AF XY: 0.267 AC XY: 19881 AN XY: 74384

African (AFR) AF: 0.0836 AC: 3475 AN: 41554

American (AMR) AF: 0.336 AC: 5137 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.444 AC: 1540 AN: 3472

East Asian (EAS) AF: 0.178 AC: 919 AN: 5176

South Asian (SAS) AF: 0.301 AC: 1451 AN: 4826

European-Finnish (FIN) AF: 0.324 AC: 3430 AN: 10580

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.341 AC: 23151 AN: 67978

Other (OTH) AF: 0.314 AC: 663 AN: 2114

Alfa AF: 0.299 Hom.: 936

Bravo AF: 0.259

Asia WGS AF: 0.269 AC: 935 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	0.12
DANN	Benign	0.63
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs12321007; hg19: chr12-124883101;