Variant chr8-133248705-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006096.4(NDRG1):c.755+10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0751 in 1,613,938 control chromosomes in the GnomAD database, including 6,378 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.065 ( 561 hom., cov: 33)

Exomes 𝑓: 0.076 ( 5817 hom. )

Consequence

NDRG1
NM_006096.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.685

Variant links:

Genes affected

NDRG1 (HGNC:7679): (N-myc downstream regulated 1) This gene is a member of the N-myc downregulated gene family which belongs to the alpha/beta hydrolase superfamily. The protein encoded by this gene is a cytoplasmic protein involved in stress responses, hormone responses, cell growth, and differentiation. The encoded protein is necessary for p53-mediated caspase activation and apoptosis. Mutations in this gene are a cause of Charcot-Marie-Tooth disease type 4D, and expression of this gene may be a prognostic indicator for several types of cancer. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, May 2012]

NDRG1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 8-133248705-A-G is Benign according to our data. Variant chr8-133248705-A-G is described in ClinVar as [Benign]. Clinvar id is 138433.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-133248705-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDRG1	NM_006096.4 linkuse as main transcript	c.755+10T>C		intron_variant		ENST00000323851.13	NP_006087.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDRG1	ENST00000323851.13 linkuse as main transcript	c.755+10T>C		intron_variant		1	NM_006096.4	ENSP00000319977	P1	Q92597-1

Frequencies

GnomAD3 genomes

AF:

0.0653

AC:

9924

AN:

152092

Hom.:

564

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0137

Gnomad AMI

AF:

0.0351

Gnomad AMR

AF:

0.0600

Gnomad ASJ

AF:

0.0375

Gnomad EAS

AF:

0.284

Gnomad SAS

AF:

0.100

Gnomad FIN

AF:

0.164

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0654

Gnomad OTH

AF:

0.0587

GnomAD3 exomes

AF:

0.0947

AC:

23805

AN:

251342

Hom.:

1742

AF XY:

0.0947

AC XY:

12871

AN XY:

135852

show subpopulations

Gnomad AFR exome

AF:

0.0112

Gnomad AMR exome

AF:

0.0948

Gnomad ASJ exome

AF:

0.0351

Gnomad EAS exome

AF:

0.298

Gnomad SAS exome

AF:

0.102

Gnomad FIN exome

AF:

0.166

Gnomad NFE exome

AF:

0.0644

Gnomad OTH exome

AF:

0.0771

GnomAD4 exome

AF:

0.0762

AC:

111358

AN:

1461726

Hom.:

5817

Cov.:

AF XY:

0.0769

AC XY:

55899

AN XY:

727180

show subpopulations

Gnomad4 AFR exome

AF:

0.0102

Gnomad4 AMR exome

AF:

0.0913

Gnomad4 ASJ exome

AF:

0.0375

Gnomad4 EAS exome

AF:

0.280

Gnomad4 SAS exome

AF:

0.104

Gnomad4 FIN exome

AF:

0.159

Gnomad4 NFE exome

AF:

0.0653

Gnomad4 OTH exome

AF:

0.0760

GnomAD4 genome

AF:

0.0652

AC:

9920

AN:

152212

Hom.:

561

Cov.:

AF XY:

0.0720

AC XY:

5361

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0136

Gnomad4 AMR

AF:

0.0602

Gnomad4 ASJ

AF:

0.0375

Gnomad4 EAS

AF:

0.284

Gnomad4 SAS

AF:

0.100

Gnomad4 FIN

AF:

0.164

Gnomad4 NFE

AF:

0.0655

Gnomad4 OTH

AF:

0.0581

Alfa

AF:

0.0590

Hom.:

340

Bravo

AF:

0.0577

Asia WGS

AF:

0.180

AC:

623

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 28, 2014	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jul 12, 2017	- -

Charcot-Marie-Tooth disease type 4D

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Charcot-Marie-Tooth disease type 4

Benign:2

Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Charcot-Marie-Tooth disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Molecular Genetics Laboratory, London Health Sciences Centre

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

9.4

DANN

Benign

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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