chr17-16101873-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_006311.4(NCOR1):​c.2183-116A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 1,307,426 control chromosomes in the GnomAD database, including 205,733 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 0.60 (27911 hom., cov: 32)
  • Exomes 𝑓: 0.55 (177822 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.72 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.2183-116A>G		intron	N/A	NP_006302.2
	NCOR1	NM_001439111.1		c.2183-68A>G		intron	N/A	NP_001426040.1
	NCOR1	NM_001439112.1		c.2213-68A>G		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.2183-116A>G		intron	N/A	ENSP00000268712.2
	NCOR1	ENST00000436068.2	TSL:1	c.2183-68A>G		intron	N/A	ENSP00000389839.2
	NCOR1	ENST00000395851.5	TSL:1	c.2183-68A>G		intron	N/A	ENSP00000379192.1

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90566 AN: 151906 Hom.: 27863 Cov.: 32

Gnomad AFR AF: 0.726

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.539

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.620

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.595

GnomAD4 exome AF: 0.547 AC: 632571 AN: 1155402 Hom.: 177822 AF XY: 0.544 AC XY: 311061 AN XY: 572060

African (AFR) AF: 0.739 AC: 19355 AN: 26174

American (AMR) AF: 0.470 AC: 12658 AN: 26910

Ashkenazi Jewish (ASJ) AF: 0.661 AC: 12819 AN: 19390

East Asian (EAS) AF: 0.182 AC: 6388 AN: 35006

South Asian (SAS) AF: 0.434 AC: 27295 AN: 62880

European-Finnish (FIN) AF: 0.601 AC: 25081 AN: 41722

Middle Eastern (MID) AF: 0.605 AC: 2345 AN: 3878

European-Non Finnish (NFE) AF: 0.561 AC: 499140 AN: 890116

Other (OTH) AF: 0.557 AC: 27490 AN: 49326

GnomAD4 genome AF: 0.596 AC: 90681 AN: 152024 Hom.: 27911 Cov.: 32 AF XY: 0.592 AC XY: 44022 AN XY: 74302

African (AFR) AF: 0.727 AC: 30130 AN: 41456

American (AMR) AF: 0.539 AC: 8232 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.668 AC: 2317 AN: 3470

East Asian (EAS) AF: 0.217 AC: 1124 AN: 5182

South Asian (SAS) AF: 0.422 AC: 2031 AN: 4816

European-Finnish (FIN) AF: 0.620 AC: 6545 AN: 10564

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.565 AC: 38384 AN: 67952

Other (OTH) AF: 0.597 AC: 1259 AN: 2110

Alfa AF: 0.555 Hom.: 14375

Bravo AF: 0.595

Asia WGS AF: 0.382 AC: 1328 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	16
DANN	Benign	0.82
PhyloP100		-0.90
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: rs2285580; hg19: chr17-16005187; COSMIC: COSV51993109; COSMIC: COSV51993109;