12-124391031-C-T

Position:

• chr12-124391031-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006312.6(NCOR2):​c.1877-5144G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 152,178 control chromosomes in the GnomAD database, including 11,592 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 0.38 (11592 hom., cov: 33)
• Consequence: NCOR2 NM_006312.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.355

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 (SAS) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCOR2	NM_006312.6	c.1877-5144G>A		intron_variant		ENST00000405201.6	NP_006303.4
NCOR2	NM_001077261.4	c.1874-5144G>A		intron_variant			NP_001070729.2
NCOR2	NM_001206654.2	c.1874-5144G>A		intron_variant			NP_001193583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCOR2	ENST00000405201.6	c.1877-5144G>A		intron_variant		1	NM_006312.6	ENSP00000384018	P4
NCOR2	ENST00000404621.5	c.1874-5144G>A		intron_variant		1		ENSP00000384202	A2
NCOR2	ENST00000429285.6	c.1874-5144G>A		intron_variant		1		ENSP00000400281	A2
NCOR2	ENST00000458234.5	c.1877-5144G>A		intron_variant		1		ENSP00000402808

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58462 AN: 152060 Hom.: 11571 Cov.: 33

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.357

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

GnomAD4 genome AF: 0.385 AC: 58531 AN: 152178 Hom.: 11592 Cov.: 33 AF XY: 0.388 AC XY: 28876 AN XY: 74408

Gnomad4 AFR AF: 0.375

Gnomad4 AMR AF: 0.398

Gnomad4 ASJ AF: 0.307

Gnomad4 EAS AF: 0.163

Gnomad4 SAS AF: 0.411

Gnomad4 FIN AF: 0.466

Gnomad4 NFE AF: 0.395

Gnomad4 OTH AF: 0.357

Alfa AF: 0.383 Hom.: 10495

Bravo AF: 0.374

Asia WGS AF: 0.340 AC: 1183 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	6.0
DANN	Benign	0.53

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: rs12708369; hg19: chr12-124875577; COSMIC: COSV62303424; COSMIC: COSV62303424;