12-124370357-G-A

Position:

• chr12-124370357-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.2807+1665C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 152,074 control chromosomes in the GnomAD database, including 19,556 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 0.47 (19556 hom., cov: 33)
• Consequence: NCOR2 NM_006312.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0640

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCOR2	NM_006312.6	c.2807+1665C>T		intron_variant		ENST00000405201.6	NP_006303.4
NCOR2	NM_001077261.4	c.2753+1665C>T		intron_variant			NP_001070729.2
NCOR2	NM_001206654.2	c.2753+1665C>T		intron_variant			NP_001193583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCOR2	ENST00000405201.6	c.2807+1665C>T		intron_variant		1	NM_006312.6	ENSP00000384018	P4
NCOR2	ENST00000404621.5	c.2753+1665C>T		intron_variant		1		ENSP00000384202	A2
NCOR2	ENST00000429285.6	c.2753+1665C>T		intron_variant		1		ENSP00000400281	A2
NCOR2	ENST00000458234.5	c.2807+1665C>T		intron_variant		1		ENSP00000402808

Frequencies

GnomAD3 genomes AF: 0.467 AC: 70914 AN: 151956 Hom.: 19549 Cov.: 33

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.712

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.643

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.555

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.608

Gnomad OTH AF: 0.507

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

GnomAD4 genome AF: 0.466 AC: 70932 AN: 152074 Hom.: 19556 Cov.: 33 AF XY: 0.465 AC XY: 34591 AN XY: 74340

Gnomad4 AFR AF: 0.182

Gnomad4 AMR AF: 0.579

Gnomad4 ASJ AF: 0.643

Gnomad4 EAS AF: 0.193

Gnomad4 SAS AF: 0.467

Gnomad4 FIN AF: 0.555

Gnomad4 NFE AF: 0.608

Gnomad4 OTH AF: 0.508

Alfa AF: 0.589 Hom.: 31876

Bravo AF: 0.459

Asia WGS AF: 0.356 AC: 1241 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.2
DANN	Benign	0.57

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: rs3782257; hg19: chr12-124854903;