rs2157991

Variant names:

• chr17-16058637-A-G
• rs2157991
• NM_006311.4:c.5882-38T>C

Your query was ambiguous. Multiple possible variants found:

• chr17-16058637-A-G
• chr17-16058637-A-T

Variant summary

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

The NM_006311.4(NCOR1):​c.5882-38T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 1,569,076 control chromosomes in the GnomAD database, including 233,802 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 (21860 hom., cov: 31)
  • Exomes 𝑓: 0.54 (211942 hom.)
• Consequence: NCOR1 NM_006311.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.651
• Publications: 17 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCOR1	NM_006311.4	c.5882-38T>C		intron_variant	Intron 37 of 45	ENST00000268712.8	NP_006302.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCOR1	ENST00000268712.8	c.5882-38T>C		intron_variant	Intron 37 of 45	1	NM_006311.4	ENSP00000268712.2

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80735 AN: 151844 Hom.: 21843 Cov.: 31

Gnomad AFR AF: 0.505

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.605

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.549

GnomAD2 exomes AF: 0.508 AC: 118584 AN: 233204 AF XY: 0.512

Gnomad AFR exome AF: 0.515

Gnomad AMR exome AF: 0.434

Gnomad ASJ exome AF: 0.669

Gnomad EAS exome AF: 0.217

Gnomad FIN exome AF: 0.599

Gnomad NFE exome AF: 0.563

Gnomad OTH exome AF: 0.552

GnomAD4 exome AF: 0.541 AC: 766911 AN: 1417114 Hom.: 211942 Cov.: 28 AF XY: 0.539 AC XY: 378066 AN XY: 701754

African (AFR) AF: 0.509 AC: 16193 AN: 31824

American (AMR) AF: 0.445 AC: 17436 AN: 39208

Ashkenazi Jewish (ASJ) AF: 0.666 AC: 16307 AN: 24492

East Asian (EAS) AF: 0.188 AC: 7354 AN: 39146

South Asian (SAS) AF: 0.431 AC: 35345 AN: 81930

European-Finnish (FIN) AF: 0.592 AC: 31046 AN: 52486

Middle Eastern (MID) AF: 0.604 AC: 3238 AN: 5360

European-Non Finnish (NFE) AF: 0.561 AC: 608530 AN: 1084424

Other (OTH) AF: 0.540 AC: 31462 AN: 58244

GnomAD4 genome AF: 0.532 AC: 80801 AN: 151962 Hom.: 21860 Cov.: 31 AF XY: 0.529 AC XY: 39284 AN XY: 74280

African (AFR) AF: 0.505 AC: 20926 AN: 41430

American (AMR) AF: 0.517 AC: 7884 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.671 AC: 2329 AN: 3470

East Asian (EAS) AF: 0.220 AC: 1137 AN: 5168

South Asian (SAS) AF: 0.418 AC: 2013 AN: 4820

European-Finnish (FIN) AF: 0.605 AC: 6369 AN: 10528

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

European-Non Finnish (NFE) AF: 0.564 AC: 38321 AN: 67972

Other (OTH) AF: 0.551 AC: 1163 AN: 2112

Alfa AF: 0.555 Hom.: 29199

Bravo AF: 0.523

Asia WGS AF: 0.361 AC: 1253 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.0
DANN	Benign	0.56
PhyloP100		-0.65
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: rs2157991; hg19: chr17-15961951; COSMIC: COSV51966321; COSMIC: COSV51966321;