rs837948

Variant names:

• chr12-124517979-G-A
• rs837948
• NM_006312.6:c.-118+17586C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCOR2	NM_006312.6	MANE Select	c.-118+17586C>T		intron	N/A	NP_006303.4	Q9Y618-1
	NCOR2	NM_001206654.2		c.-118+17586C>T		intron	N/A	NP_001193583.1	C9J0Q5
	NCOR2	NM_001077261.4		c.-118+17586C>T		intron	N/A	NP_001070729.2	C9JE98

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCOR2	ENST00000405201.6	TSL:1 MANE Select	c.-118+17586C>T		intron	N/A	ENSP00000384018.1	Q9Y618-1
	NCOR2	ENST00000429285.6	TSL:1	c.-118+17586C>T		intron	N/A	ENSP00000400281.2	C9J0Q5
	NCOR2	ENST00000404621.5	TSL:1	c.-118+17586C>T		intron	N/A	ENSP00000384202.1	C9JE98

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

African (AFR) AF: 0.107 AC: 4413 AN: 41380

American (AMR) AF: 0.376 AC: 5747 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.366 AC: 1268 AN: 3466

East Asian (EAS) AF: 0.464 AC: 2357 AN: 5078

South Asian (SAS) AF: 0.325 AC: 1561 AN: 4798

European-Finnish (FIN) AF: 0.408 AC: 4291 AN: 10516

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.324 AC: 21995 AN: 67852

Other (OTH) AF: 0.322 AC: 677 AN: 2100

Alfa AF: 0.314 Hom.: 12988

Bravo AF: 0.273

Asia WGS AF: 0.386 AC: 1346 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.62
DANN	Benign	0.80
PhyloP100		-0.41
PromoterAI		0.0010	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs837948; hg19: chr12-125002525;