chr12-124517777-C-T

Variant names:

• chr12-124517777-C-T
• rs150954431
• NM_006312.6:c.-118+17788G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_006312.6(NCOR2):​c.-118+17788G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0156 in 152,336 control chromosomes in the GnomAD database, including 40 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 0.016 (40 hom., cov: 32)
• Consequence: NCOR2 NM_006312.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.58
• Publications: 5 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]

ENSG00000303311 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0156 (2380/152336) while in subpopulation NFE AF = 0.0219 (1493/68020). AF 95% confidence interval is 0.021. There are 40 homozygotes in GnomAd4. There are 1077 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2380 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006312.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCOR2	NM_006312.6	MANE Select	c.-118+17788G>A		intron	N/A	NP_006303.4
	NCOR2	NM_001206654.2		c.-118+17788G>A		intron	N/A	NP_001193583.1
	NCOR2	NM_001077261.4		c.-118+17788G>A		intron	N/A	NP_001070729.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCOR2	ENST00000405201.6	TSL:1 MANE Select	c.-118+17788G>A		intron	N/A	ENSP00000384018.1
	NCOR2	ENST00000429285.6	TSL:1	c.-118+17788G>A		intron	N/A	ENSP00000400281.2
	NCOR2	ENST00000404621.5	TSL:1	c.-118+17788G>A		intron	N/A	ENSP00000384202.1

Frequencies

GnomAD3 genomes AF: 0.0156 AC: 2380 AN: 152218 Hom.: 40 Cov.: 32

Gnomad AFR AF: 0.00386

Gnomad AMI AF: 0.00549

Gnomad AMR AF: 0.0124

Gnomad ASJ AF: 0.0847

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00434

Gnomad FIN AF: 0.0150

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0220

Gnomad OTH AF: 0.0211

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

GnomAD4 genome AF: 0.0156 AC: 2380 AN: 152336 Hom.: 40 Cov.: 32 AF XY: 0.0145 AC XY: 1077 AN XY: 74496

African (AFR) AF: 0.00385 AC: 160 AN: 41582

American (AMR) AF: 0.0123 AC: 189 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.0847 AC: 294 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00455 AC: 22 AN: 4830

European-Finnish (FIN) AF: 0.0150 AC: 159 AN: 10622

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0219 AC: 1493 AN: 68020

Other (OTH) AF: 0.0208 AC: 44 AN: 2112

Alfa AF: 0.0164 Hom.: 4

Bravo AF: 0.0160

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.2
DANN	Benign	0.93
PhyloP100		-2.6
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs150954431; hg19: chr12-125002323;