17-16101873-T-C

Position:

• chr17-16101873-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCOR1	NM_006311.4	c.2183-116A>G		intron_variant		ENST00000268712.8	NP_006302.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCOR1	ENST00000268712.8	c.2183-116A>G		intron_variant		1	NM_006311.4	ENSP00000268712	P3

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

Gnomad4 AFR exome AF: 0.739

Gnomad4 AMR exome AF: 0.470

Gnomad4 ASJ exome AF: 0.661

Gnomad4 EAS exome AF: 0.182

Gnomad4 SAS exome AF: 0.434

Gnomad4 FIN exome AF: 0.601

Gnomad4 NFE exome AF: 0.561

Gnomad4 OTH exome AF: 0.557

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

Gnomad4 AFR AF: 0.727

Gnomad4 AMR AF: 0.539

Gnomad4 ASJ AF: 0.668

Gnomad4 EAS AF: 0.217

Gnomad4 SAS AF: 0.422

Gnomad4 FIN AF: 0.620

Gnomad4 NFE AF: 0.565

Gnomad4 OTH AF: 0.597

Alfa AF: 0.551 Hom.: 12869

Bravo AF: 0.595

Asia WGS AF: 0.382 AC: 1328 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	16
DANN	Benign	0.82

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

Publications

LitVar

Other links and lift over

dbSNP: rs2285580; hg19: chr17-16005187; COSMIC: COSV51993109; COSMIC: COSV51993109;