NM_006311.4:c.2183-116A>T

Variant names:

• chr17-16101873-T-A
• rs2285580
• NM_006311.4:c.2183-116A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006311.4(NCOR1):​c.2183-116A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000863 in 1,158,170 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 8.6e-7 (0 hom.)
• Consequence: NCOR1 NM_006311.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.898
• Publications: 16 publications found

Genes affected

NCOR1 (HGNC:7672): (nuclear receptor corepressor 1) This gene encodes a protein that mediates ligand-independent transcription repression of thyroid-hormone and retinoic-acid receptors by promoting chromatin condensation and preventing access of the transcription machinery. It is part of a complex which also includes histone deacetylases and transcriptional regulators similar to the yeast protein Sin3p. This gene is located between the Charcot-Marie-Tooth and Smith-Magenis syndrome critical regions on chromosome 17. Alternate splicing results in multiple transcript variants. Pseudogenes of this gene are found on chromosomes 17 and 20.[provided by RefSeq, Jun 2010]

NCOR1 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCOR1	NM_006311.4	c.2183-116A>T		intron_variant	Intron 19 of 45	ENST00000268712.8	NP_006302.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCOR1	ENST00000268712.8	c.2183-116A>T		intron_variant	Intron 19 of 45	1	NM_006311.4	ENSP00000268712.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.63e-7 AC: 1 AN: 1158170 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 573384

African (AFR) AF: 0.00 AC: 0 AN: 26200

American (AMR) AF: 0.00 AC: 0 AN: 26938

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19410

East Asian (EAS) AF: 0.00 AC: 0 AN: 35014

South Asian (SAS) AF: 0.00 AC: 0 AN: 62966

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41794

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3896

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 892514

Other (OTH) AF: 0.0000202 AC: 1 AN: 49438

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 14375

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	15
DANN	Benign	0.80
PhyloP100		-0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs2285580; hg19: chr17-16005187;