Genetic Variant NCOR1:c.108+346G>A (chr17-16194116-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.137

Publications

19 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006311.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NCOR1	NM_006311.4	MANE Select	c.108+346G>A	intron	N/A	NP_006302.2
NCOR1	NM_001439111.1		c.108+346G>A	intron	N/A	NP_001426040.1
NCOR1	NM_001439112.1		c.108+346G>A	intron	N/A	NP_001426041.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NCOR1	ENST00000268712.8	TSL:1 MANE Select	c.108+346G>A	intron	N/A	ENSP00000268712.2	O75376-1
NCOR1	ENST00000436068.2	TSL:1	c.108+346G>A	intron	N/A	ENSP00000389839.2	H0Y459
NCOR1	ENST00000395851.5	TSL:1	c.108+346G>A	intron	N/A	ENSP00000379192.1	O75376-2

Frequencies

GnomAD3 genomes

AF:

0.531

AC:

80620

AN:

151768

Hom.:

21808

Cov.:

show subpopulations

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.:

AF XY:

0.529

AC XY:

39282

AN XY:

74244

show subpopulations

African (AFR)

AF:

0.499

AC:

20652

AN:

41376

American (AMR)

AF:

0.515

AC:

7842

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.668

AC:

2316

AN:

3468

East Asian (EAS)

AF:

0.217

AC:

1121

AN:

5176

South Asian (SAS)

AF:

0.422

AC:

2031

AN:

4812

European-Finnish (FIN)

AF:

0.621

AC:

6550

AN:

10544

Middle Eastern (MID)

AF:

0.612

AC:

180

AN:

294

European-Non Finnish (NFE)

AF:

0.564

AC:

38351

AN:

67958

Other (OTH)

AF:

0.549

AC:

1161

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1887

3774

5660

7547

9434

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

708

1416

2124

2832

3540

<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:

0.551

Hom.:

17742

Bravo

AF:

0.520

Asia WGS

AF:

0.361

AC:

1254

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

5.8

(source)

DANN

Benign

0.19

PhyloP100

0.14

PromoterAI

-0.036

Neutral

(source)

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over