12-124499070-T-C

Position:

• chr12-124499070-T-C

Variant summary

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

The ENST00000405201.6(NCOR2):​c.-117-3702A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.8 in 152,268 control chromosomes in the GnomAD database, including 48,943 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 0.80 (48943 hom., cov: 33)
• Consequence: NCOR2 ENST00000405201.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.543

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCOR2	NM_006312.6	c.-117-3702A>G		intron_variant		ENST00000405201.6	NP_006303.4
NCOR2	NM_001077261.4	c.-117-3702A>G		intron_variant			NP_001070729.2
NCOR2	NM_001206654.2	c.-117-3702A>G		intron_variant			NP_001193583.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCOR2	ENST00000405201.6	c.-117-3702A>G		intron_variant		1	NM_006312.6	ENSP00000384018	P4

Frequencies

GnomAD3 genomes AF: 0.800 AC: 121777 AN: 152152 Hom.: 48890 Cov.: 33

Gnomad AFR AF: 0.777

Gnomad AMI AF: 0.678

Gnomad AMR AF: 0.835

Gnomad ASJ AF: 0.756

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.869

Gnomad FIN AF: 0.850

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.783

Gnomad OTH AF: 0.798

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

GnomAD4 genome AF: 0.800 AC: 121890 AN: 152268 Hom.: 48943 Cov.: 33 AF XY: 0.807 AC XY: 60094 AN XY: 74468

Gnomad4 AFR AF: 0.778

Gnomad4 AMR AF: 0.835

Gnomad4 ASJ AF: 0.756

Gnomad4 EAS AF: 0.995

Gnomad4 SAS AF: 0.869

Gnomad4 FIN AF: 0.850

Gnomad4 NFE AF: 0.783

Gnomad4 OTH AF: 0.799

Alfa AF: 0.785 Hom.: 54634

Bravo AF: 0.798

Asia WGS AF: 0.925 AC: 3213 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.3
DANN	Benign	0.51

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1110904; hg19: chr12-124983616;