rs1305047

Variant names:

• chr17-16181671-A-AACAC
• rs1305047
• NM_006311.4:c.242+4879_242+4882dupGTGT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_006311.4(NCOR1):​c.242+4879_242+4882dupGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.46 (17035 hom., cov: 0)
• Consequence: NCOR1 NM_006311.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347
• Publications: 7 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: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCOR1	NM_006311.4	c.242+4879_242+4882dupGTGT		intron_variant	Intron 3 of 45	ENST00000268712.8	NP_006302.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCOR1	ENST00000268712.8	c.242+4882_242+4883insGTGT		intron_variant	Intron 3 of 45	1	NM_006311.4	ENSP00000268712.2

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70121 AN: 151534 Hom.: 17023 Cov.: 0

Gnomad AFR AF: 0.368

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.610

Gnomad EAS AF: 0.0958

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.477

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

GnomAD4 genome AF: 0.463 AC: 70180 AN: 151652 Hom.: 17035 Cov.: 0 AF XY: 0.460 AC XY: 34089 AN XY: 74084

African (AFR) AF: 0.368 AC: 15226 AN: 41352

American (AMR) AF: 0.455 AC: 6942 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.610 AC: 2114 AN: 3464

East Asian (EAS) AF: 0.0961 AC: 498 AN: 5184

South Asian (SAS) AF: 0.342 AC: 1641 AN: 4804

European-Finnish (FIN) AF: 0.570 AC: 5950 AN: 10430

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.533 AC: 36158 AN: 67856

Other (OTH) AF: 0.479 AC: 1012 AN: 2114

Alfa AF: 0.494 Hom.: 2298

Bravo AF: 0.449

Asia WGS AF: 0.252 AC: 872 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.35
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: rs1305047; hg19: chr17-16084985;