chr12-124398555-G-A

Position:

• chr12-124398555-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.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

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=-0.86).
• 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/exons	MANE	Protein	UniProt
NCOR2	NM_006312.6	c.1814-374C>T		intron_variant		ENST00000405201.6	NP_006303.4
NCOR2	NM_001077261.4	c.1811-374C>T		intron_variant			NP_001070729.2
NCOR2	NM_001206654.2	c.1811-374C>T		intron_variant			NP_001193583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCOR2	ENST00000405201.6	c.1814-374C>T		intron_variant		1	NM_006312.6	ENSP00000384018	P4
NCOR2	ENST00000404621.5	c.1811-374C>T		intron_variant		1		ENSP00000384202	A2
NCOR2	ENST00000429285.6	c.1811-374C>T		intron_variant		1		ENSP00000400281	A2
NCOR2	ENST00000458234.5	c.1814-374C>T		intron_variant		1		ENSP00000402808

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

Gnomad4 AFR AF: 0.0836

Gnomad4 AMR AF: 0.336

Gnomad4 ASJ AF: 0.444

Gnomad4 EAS AF: 0.178

Gnomad4 SAS AF: 0.301

Gnomad4 FIN AF: 0.324

Gnomad4 NFE AF: 0.341

Gnomad4 OTH AF: 0.314

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs12321007; hg19: chr12-124883101;