chr12-124409638-T-C

Position:

• chr12-124409638-T-C

Variant summary

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

The NM_006312.6(NCOR2):​c.1483-7077A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 151,774 control chromosomes in the GnomAD database, including 4,136 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 0.23 (4136 hom., cov: 31)
• Consequence: NCOR2 NM_006312.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.366

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCOR2	NM_006312.6	c.1483-7077A>G		intron_variant		ENST00000405201.6	NP_006303.4
NCOR2	NM_001077261.4	c.1480-7077A>G		intron_variant			NP_001070729.2
NCOR2	NM_001206654.2	c.1480-7077A>G		intron_variant			NP_001193583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCOR2	ENST00000405201.6	c.1483-7077A>G		intron_variant		1	NM_006312.6	ENSP00000384018	P4
NCOR2	ENST00000404621.5	c.1480-7077A>G		intron_variant		1		ENSP00000384202	A2
NCOR2	ENST00000429285.6	c.1480-7077A>G		intron_variant		1		ENSP00000400281	A2
NCOR2	ENST00000458234.5	c.1483-7077A>G		intron_variant		1		ENSP00000402808

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34607 AN: 151654 Hom.: 4116 Cov.: 31

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.236

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

GnomAD4 genome AF: 0.228 AC: 34669 AN: 151774 Hom.: 4136 Cov.: 31 AF XY: 0.226 AC XY: 16737 AN XY: 74150

Gnomad4 AFR AF: 0.249

Gnomad4 AMR AF: 0.286

Gnomad4 ASJ AF: 0.225

Gnomad4 EAS AF: 0.284

Gnomad4 SAS AF: 0.258

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.210

Gnomad4 OTH AF: 0.243

Alfa AF: 0.210 Hom.: 3233

Bravo AF: 0.240

Asia WGS AF: 0.274 AC: 950 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.0
DANN	Benign	0.58

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: rs12582168; hg19: chr12-124894184;