chr12-124549804-G-A

Variant names:

• chr12-124549804-G-A
• rs10846684
• NM_006312.6:c.-164-14193C>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.-164-14193C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 152,114 control chromosomes in the GnomAD database, including 3,550 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 0.21 (3550 hom., cov: 32)
• Consequence: NCOR2 NM_006312.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.13
• Publications: 7 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCOR2	NM_006312.6	c.-164-14193C>T		intron_variant	Intron 1 of 48	ENST00000405201.6	NP_006303.4
NCOR2	NM_001206654.2	c.-164-14193C>T		intron_variant	Intron 1 of 47		NP_001193583.1
NCOR2	NM_001077261.4	c.-164-14193C>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.-164-14193C>T		intron_variant	Intron 1 of 48	1	NM_006312.6	ENSP00000384018.1
NCOR2	ENST00000458234.5	c.-164-14193C>T		intron_variant	Intron 1 of 32	1		ENSP00000402808.1
NCOR2	ENST00000542565.1	n.283-14193C>T		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32160 AN: 151996 Hom.: 3541 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.212 AC: 32177 AN: 152114 Hom.: 3550 Cov.: 32 AF XY: 0.210 AC XY: 15587 AN XY: 74350

African (AFR) AF: 0.187 AC: 7736 AN: 41472

American (AMR) AF: 0.244 AC: 3732 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 809 AN: 3472

East Asian (EAS) AF: 0.169 AC: 876 AN: 5172

South Asian (SAS) AF: 0.249 AC: 1202 AN: 4820

European-Finnish (FIN) AF: 0.176 AC: 1862 AN: 10600

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.223 AC: 15138 AN: 67962

Other (OTH) AF: 0.207 AC: 437 AN: 2112

Alfa AF: 0.217 Hom.: 5646

Bravo AF: 0.217

Asia WGS AF: 0.211 AC: 735 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.033
DANN	Benign	0.74
PhyloP100		-2.1

Splicing

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

Other links and lift over

dbSNP: rs10846684; hg19: chr12-125034350;