rs178814

Positions:

• chr17-16190841-G-C
• chr17-16190841-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006311.4(NCOR1):​c.108+3621C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 152,118 control chromosomes in the GnomAD database, including 25,891 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 0.58 (25891 hom., cov: 32)
• Consequence: NCOR1 NM_006311.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.104

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCOR1	NM_006311.4	c.108+3621C>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.108+3621C>G		intron_variant		1	NM_006311.4	ENSP00000268712	P3

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87664 AN: 151996 Hom.: 25866 Cov.: 32

Gnomad AFR AF: 0.659

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.530

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.619

Gnomad MID AF: 0.621

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.577

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

GnomAD4 genome AF: 0.577 AC: 87749 AN: 152118 Hom.: 25891 Cov.: 32 AF XY: 0.573 AC XY: 42594 AN XY: 74354

Gnomad4 AFR AF: 0.659

Gnomad4 AMR AF: 0.531

Gnomad4 ASJ AF: 0.668

Gnomad4 EAS AF: 0.217

Gnomad4 SAS AF: 0.423

Gnomad4 FIN AF: 0.619

Gnomad4 NFE AF: 0.565

Gnomad4 OTH AF: 0.579

Alfa AF: 0.428 Hom.: 1080

Bravo AF: 0.573

Asia WGS AF: 0.371 AC: 1291 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.46
DANN	Benign	0.50

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: rs178814; hg19: chr17-16094155; COSMIC: COSV51967912; COSMIC: COSV51967912;