12-124325588-G-A

Variant names:

• chr12-124325588-G-A
• rs189013704
• NM_006312.6:c.7364-5C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_006312.6(NCOR2):​c.7364-5C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0011 in 1,273,698 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00058 (1 hom., cov: 30)
  • Exomes 𝑓: 0.0012 (0 hom.)
• Consequence: NCOR2 NM_006312.6 splice_region, intron
• Scores: Splicing: ADA: 0.000007971
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.562
• Publications: 0 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]

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 12-124325588-G-A is Benign according to our data. Variant chr12-124325588-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3052029.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd4 at 88 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCOR2	NM_006312.6	MANE Select	c.7364-5C>T		splice_region intron	N/A	NP_006303.4	Q9Y618-1
	NCOR2	NM_001206654.2		c.7334-5C>T		splice_region intron	N/A	NP_001193583.1	C9J0Q5
	NCOR2	NM_001077261.4		c.7196-5C>T		splice_region 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.7364-5C>T		splice_region intron	N/A	ENSP00000384018.1	Q9Y618-1
	NCOR2	ENST00000429285.6	TSL:1	c.7334-5C>T		splice_region intron	N/A	ENSP00000400281.2	C9J0Q5
	NCOR2	ENST00000404621.5	TSL:1	c.7196-5C>T		splice_region intron	N/A	ENSP00000384202.1	C9JE98

Frequencies

GnomAD3 genomes AF: 0.000579 AC: 88 AN: 152048 Hom.: 1 Cov.: 30

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000868

Gnomad OTH AF: 0.000959

GnomAD2 exomes AF: 0.000377 AC: 11 AN: 29182 AF XY: 0.000497

Gnomad AFR exome AF: 0.000362

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000393

Gnomad NFE exome AF: 0.000410

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00117 AC: 1309 AN: 1121532 Hom.: 0 Cov.: 37 AF XY: 0.00120 AC XY: 638 AN XY: 533068

African (AFR) AF: 0.000454 AC: 11 AN: 24208

American (AMR) AF: 0.000114 AC: 1 AN: 8772

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14644

East Asian (EAS) AF: 0.00 AC: 0 AN: 28322

South Asian (SAS) AF: 0.00103 AC: 28 AN: 27228

European-Finnish (FIN) AF: 0.000487 AC: 18 AN: 36994

Middle Eastern (MID) AF: 0.000988 AC: 4 AN: 4050

European-Non Finnish (NFE) AF: 0.00129 AC: 1204 AN: 932486

Other (OTH) AF: 0.000959 AC: 43 AN: 44828

GnomAD4 genome AF: 0.000578 AC: 88 AN: 152166 Hom.: 1 Cov.: 30 AF XY: 0.000470 AC XY: 35 AN XY: 74398

African (AFR) AF: 0.000337 AC: 14 AN: 41538

American (AMR) AF: 0.000262 AC: 4 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5150

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4824

European-Finnish (FIN) AF: 0.000471 AC: 5 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000868 AC: 59 AN: 67968

Other (OTH) AF: 0.000949 AC: 2 AN: 2108

Alfa AF: 0.000651 Hom.: 0

Bravo AF: 0.000461

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	NCOR2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.83
DANN	Benign	0.54
PhyloP100		-0.56
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0000080
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs189013704; hg19: chr12-124810134;