17-16189615-C-T

Variant names:

• chr17-16189615-C-T
• rs178815
• NM_006311.4:c.109-2928G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006311.4(NCOR1):​c.109-2928G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 151,838 control chromosomes in the GnomAD database, including 21,818 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 0.53 (21818 hom., cov: 31)
• Consequence: NCOR1 NM_006311.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.370
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006311.4. 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
	NCOR1	NM_006311.4	MANE Select	c.109-2928G>A		intron	N/A	NP_006302.2
	NCOR1	NM_001439111.1		c.109-2928G>A		intron	N/A	NP_001426040.1
	NCOR1	NM_001439112.1		c.109-2928G>A		intron	N/A	NP_001426041.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCOR1	ENST00000268712.8	TSL:1 MANE Select	c.109-2928G>A		intron	N/A	ENSP00000268712.2	O75376-1
	NCOR1	ENST00000436068.2	TSL:1	c.109-2928G>A		intron	N/A	ENSP00000389839.2	H0Y459
	NCOR1	ENST00000395851.5	TSL:1	c.109-2928G>A		intron	N/A	ENSP00000379192.1	O75376-2

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80604 AN: 151720 Hom.: 21802 Cov.: 31

Gnomad AFR AF: 0.500

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.620

Gnomad MID AF: 0.618

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.548

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

GnomAD4 genome AF: 0.531 AC: 80663 AN: 151838 Hom.: 21818 Cov.: 31 AF XY: 0.529 AC XY: 39263 AN XY: 74202

African (AFR) AF: 0.500 AC: 20681 AN: 41388

American (AMR) AF: 0.515 AC: 7860 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.668 AC: 2316 AN: 3466

East Asian (EAS) AF: 0.217 AC: 1121 AN: 5174

South Asian (SAS) AF: 0.423 AC: 2031 AN: 4806

European-Finnish (FIN) AF: 0.620 AC: 6512 AN: 10498

Middle Eastern (MID) AF: 0.610 AC: 178 AN: 292

European-Non Finnish (NFE) AF: 0.564 AC: 38331 AN: 67934

Other (OTH) AF: 0.549 AC: 1156 AN: 2104

Alfa AF: 0.462 Hom.: 1828

Bravo AF: 0.520

Asia WGS AF: 0.362 AC: 1255 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.51
DANN	Benign	0.36
PhyloP100		-0.37
Mutation Taster		=100/0	polymorphism (auto)

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: rs178815; hg19: chr17-16092929; COSMIC: COSV51967904; COSMIC: COSV51967904;