Variant 17-16047086-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_006311.4(NCOR1):c.6544G>A(p.Ala2182Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00982 in 1,611,402 control chromosomes in the GnomAD database, including 96 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0066 ( 10 hom., cov: 32)

Exomes 𝑓: 0.010 ( 86 hom. )

Consequence

NCOR1
NM_006311.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 6.87

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0074718).

BP6

Variant 17-16047086-C-T is Benign according to our data. Variant chr17-16047086-C-T is described in ClinVar as [Benign]. Clinvar id is 771023.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 1007 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCOR1	NM_006311.4 linkuse as main transcript	c.6544G>A	p.Ala2182Thr	missense_variant	42/46	ENST00000268712.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCOR1	ENST00000268712.8 linkuse as main transcript	c.6544G>A	p.Ala2182Thr	missense_variant	42/46	1	NM_006311.4	P3	O75376-1

Frequencies

GnomAD3 genomes

AF:

0.00662

AC:

1007

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00167

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00439

Gnomad ASJ

AF:

0.00663

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00480

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0114

Gnomad OTH

AF:

0.00766

GnomAD3 exomes

AF:

0.00667

AC:

1641

AN:

245970

Hom.:

AF XY:

0.00674

AC XY:

897

AN XY:

133136

show subpopulations

Gnomad AFR exome

AF:

0.00136

Gnomad AMR exome

AF:

0.00231

Gnomad ASJ exome

AF:

0.00811

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000766

Gnomad FIN exome

AF:

0.00562

Gnomad NFE exome

AF:

0.0114

Gnomad OTH exome

AF:

0.00961

GnomAD4 exome

AF:

0.0102

AC:

14818

AN:

1459136

Hom.:

Cov.:

AF XY:

0.0100

AC XY:

7275

AN XY:

725810

show subpopulations

Gnomad4 AFR exome

AF:

0.00126

Gnomad4 AMR exome

AF:

0.00255

Gnomad4 ASJ exome

AF:

0.00682

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00100

Gnomad4 FIN exome

AF:

0.00613

Gnomad4 NFE exome

AF:

0.0122

Gnomad4 OTH exome

AF:

0.00805

GnomAD4 genome

AF:

0.00661

AC:

1007

AN:

152266

Hom.:

Cov.:

AF XY:

0.00614

AC XY:

457

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00166

Gnomad4 AMR

AF:

0.00438

Gnomad4 ASJ

AF:

0.00663

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00480

Gnomad4 NFE

AF:

0.0114

Gnomad4 OTH

AF:

0.00758

Alfa

AF:

0.0107

Hom.:

Bravo

AF:

0.00647

TwinsUK

AF:

0.0116

AC:

ALSPAC

AF:

0.0112

AC:

ESP6500AA

AF:

0.00250

AC:

ESP6500EA

AF:

0.0121

AC:

104

ExAC

AF:

0.00725

AC:

880

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0109

EpiControl

AF:

0.0110

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2024	NCOR1: BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 26, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

NCOR1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 25, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.34

T;.;.

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.10

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.96

D;D;D

MetaRNN

Benign

0.0075

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.;.

MutationTaster

Benign

0.98

N;N;N

PrimateAI

Uncertain

0.62

PROVEAN

Benign

0.030

N;.;N

REVEL

Benign

0.13

Sift

Uncertain

0.0010

D;.;D

Sift4G

Uncertain

0.024

D;D;D

Polyphen

0.0

B;.;B

Vest4

0.23

MVP

0.43

MPC

0.28

ClinPred

0.048

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.20

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over