chr17-16194116-C-T

Position:

• chr17-16194116-C-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+346G>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 151,886 control chromosomes in the GnomAD database, including 21,824 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 (21824 hom., cov: 31)
• Consequence: NCOR1 NM_006311.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.137

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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCOR1	NM_006311.4	c.108+346G>A		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+346G>A		intron_variant		1	NM_006311.4	ENSP00000268712	P3

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80620 AN: 151768 Hom.: 21808 Cov.: 31

Gnomad AFR AF: 0.500

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.547

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

GnomAD4 genome AF: 0.531 AC: 80679 AN: 151886 Hom.: 21824 Cov.: 31 AF XY: 0.529 AC XY: 39282 AN XY: 74244

Gnomad4 AFR AF: 0.499

Gnomad4 AMR AF: 0.515

Gnomad4 ASJ AF: 0.668

Gnomad4 EAS AF: 0.217

Gnomad4 SAS AF: 0.422

Gnomad4 FIN AF: 0.621

Gnomad4 NFE AF: 0.564

Gnomad4 OTH AF: 0.549

Alfa AF: 0.556 Hom.: 14431

Bravo AF: 0.520

Asia WGS AF: 0.361 AC: 1254 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	5.8
DANN	Benign	0.19

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: rs178810; hg19: chr17-16097430;