rs150954431

chr12-124517777-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.82).
• 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 male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 2380 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCOR2	NM_006312.6	c.-118+17788G>A		intron_variant		ENST00000405201.6
NCOR2	NM_001077261.4	c.-118+17788G>A		intron_variant
NCOR2	NM_001206654.2	c.-118+17788G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCOR2	ENST00000405201.6	c.-118+17788G>A		intron_variant		1	NM_006312.6	P4

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

Gnomad4 AFR AF: 0.00385

Gnomad4 AMR AF: 0.0123

Gnomad4 ASJ AF: 0.0847

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00455

Gnomad4 FIN AF: 0.0150

Gnomad4 NFE AF: 0.0219

Gnomad4 OTH AF: 0.0208

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	2.2
Dann	Benign	0.93

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs150954431; hg19: chr12-125002323;