12-124399878-C-T

Variant names:

• chr12-124399878-C-T
• rs10846667
• NM_006312.6:c.1813+623G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006312.6(NCOR2):​c.1813+623G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 151,958 control chromosomes in the GnomAD database, including 12,923 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 (12923 hom., cov: 31)
• Consequence: NCOR2 NM_006312.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.83
• Publications: 6 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCOR2	NM_006312.6	c.1813+623G>A		intron_variant	Intron 17 of 48	ENST00000405201.6	NP_006303.4
NCOR2	NM_001206654.2	c.1810+623G>A		intron_variant	Intron 17 of 47		NP_001193583.1
NCOR2	NM_001077261.4	c.1810+623G>A		intron_variant	Intron 17 of 47		NP_001070729.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCOR2	ENST00000405201.6	c.1813+623G>A		intron_variant	Intron 17 of 48	1	NM_006312.6	ENSP00000384018.1
NCOR2	ENST00000429285.6	c.1810+623G>A		intron_variant	Intron 16 of 46	1		ENSP00000400281.2
NCOR2	ENST00000404621.5	c.1810+623G>A		intron_variant	Intron 16 of 46	1		ENSP00000384202.1
NCOR2	ENST00000458234.5	c.1813+623G>A		intron_variant	Intron 17 of 32	1		ENSP00000402808.1

Frequencies

GnomAD3 genomes AF: 0.375 AC: 57009 AN: 151838 Hom.: 12918 Cov.: 31

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.601

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.416

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

GnomAD4 genome AF: 0.375 AC: 57024 AN: 151958 Hom.: 12923 Cov.: 31 AF XY: 0.379 AC XY: 28157 AN XY: 74278

African (AFR) AF: 0.131 AC: 5439 AN: 41442

American (AMR) AF: 0.432 AC: 6611 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 1939 AN: 3470

East Asian (EAS) AF: 0.182 AC: 938 AN: 5166

South Asian (SAS) AF: 0.342 AC: 1645 AN: 4812

European-Finnish (FIN) AF: 0.539 AC: 5678 AN: 10532

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.489 AC: 33223 AN: 67934

Other (OTH) AF: 0.418 AC: 882 AN: 2110

Alfa AF: 0.451 Hom.: 30394

Bravo AF: 0.357

Asia WGS AF: 0.292 AC: 1017 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.15
DANN	Benign	0.80
PhyloP100		-2.8
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: rs10846667; hg19: chr12-124884424;