Genetic Variant NCOR1:c.2183-116A>G (chr17-16101873-T-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.898

Publications

16 publications found

Variant links:

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

NCOR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCOR1	NM_006311.4 link	c.2183-116A>G		intron_variant	Intron 19 of 45	ENST00000268712.8	NP_006302.2	O75376-1A0A024RD47

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCOR1	ENST00000268712.8 link	c.2183-116A>G		intron_variant	Intron 19 of 45	1	NM_006311.4	ENSP00000268712.2		O75376-1

Frequencies

GnomAD3 genomes

AF:

0.596

AC:

90566

AN:

151906

Hom.:

27863

Cov.:

show subpopulations

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

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

14361

28723

43084

57446

71807

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13522

27044

40566

54088

67610

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.596

AC:

90681

AN:

152024

Hom.:

27911

Cov.:

AF XY:

0.592

AC XY:

44022

AN XY:

74302

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1790

3580

5371

7161

8951

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

748

1496

2244

2992

3740

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.82

PhyloP100

-0.90

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over