rs906304

Variant names:

• chr12-124441597-G-A
• rs906304
• NM_006312.6:c.816-3601C>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.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
• Publications: 9 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=-0.84).
• 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 rank	MANE	Protein	UniProt
NCOR2	NM_006312.6	c.816-3601C>T		intron_variant	Intron 9 of 48	ENST00000405201.6	NP_006303.4
NCOR2	NM_001206654.2	c.816-3601C>T		intron_variant	Intron 9 of 47		NP_001193583.1
NCOR2	NM_001077261.4	c.816-3601C>T		intron_variant	Intron 9 of 47		NP_001070729.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCOR2	ENST00000405201.6	c.816-3601C>T		intron_variant	Intron 9 of 48	1	NM_006312.6	ENSP00000384018.1

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

African (AFR) AF: 0.125 AC: 5207 AN: 41534

American (AMR) AF: 0.170 AC: 2596 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0980 AC: 340 AN: 3470

East Asian (EAS) AF: 0.216 AC: 1119 AN: 5174

South Asian (SAS) AF: 0.130 AC: 627 AN: 4824

European-Finnish (FIN) AF: 0.0605 AC: 642 AN: 10606

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9691 AN: 68010

Other (OTH) AF: 0.157 AC: 330 AN: 2106

Alfa AF: 0.146 Hom.: 3221

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
PhyloP100		0.49
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs906304; hg19: chr12-124926143;