rs906304

chr12-124441597-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.816-3601C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,208 control chromosomes in the GnomAD database, including 1,446 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 0.14 (1446 hom., cov: 33)
• Consequence: NCOR2 NM_006312.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.486

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCOR2	NM_006312.6	c.816-3601C>T		intron_variant		ENST00000405201.6
NCOR2	NM_001077261.4	c.816-3601C>T		intron_variant
NCOR2	NM_001206654.2	c.816-3601C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCOR2	ENST00000405201.6	c.816-3601C>T		intron_variant		1	NM_006312.6	P4

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20683 AN: 152090 Hom.: 1437 Cov.: 33

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.0980

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.0605

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.136 AC: 20704 AN: 152208 Hom.: 1446 Cov.: 33 AF XY: 0.133 AC XY: 9884 AN XY: 74410

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.0980

Gnomad4 EAS AF: 0.216

Gnomad4 SAS AF: 0.130

Gnomad4 FIN AF: 0.0605

Gnomad4 NFE AF: 0.142

Gnomad4 OTH AF: 0.157

Alfa AF: 0.146 Hom.: 2340

Bravo AF: 0.145

Asia WGS AF: 0.155 AC: 538 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	8.4
Dann	Benign	0.91

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: rs906304; hg19: chr12-124926143;