rs837948

Positions:

• chr12-124517979-G-A
• chr12-124517979-G-T

Variant summary

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

The NM_006312.6(NCOR2):​c.-118+17586C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 151,658 control chromosomes in the GnomAD database, including 6,930 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 0.28 (6930 hom., cov: 31)
• Consequence: NCOR2 NM_006312.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.409

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCOR2	NM_006312.6	c.-118+17586C>T		intron_variant		ENST00000405201.6
NCOR2	NM_001077261.4	c.-118+17586C>T		intron_variant
NCOR2	NM_001206654.2	c.-118+17586C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCOR2	ENST00000405201.6	c.-118+17586C>T		intron_variant		1	NM_006312.6	P4

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42457 AN: 151540 Hom.: 6928 Cov.: 31

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.0716

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.321

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

GnomAD4 genome AF: 0.280 AC: 42465 AN: 151658 Hom.: 6930 Cov.: 31 AF XY: 0.288 AC XY: 21325 AN XY: 74064

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.376

Gnomad4 ASJ AF: 0.366

Gnomad4 EAS AF: 0.464

Gnomad4 SAS AF: 0.325

Gnomad4 FIN AF: 0.408

Gnomad4 NFE AF: 0.324

Gnomad4 OTH AF: 0.322

Alfa AF: 0.318 Hom.: 10447

Bravo AF: 0.273

Asia WGS AF: 0.386 AC: 1346 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.62
DANN	Benign	0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs837948; hg19: chr12-125002525;