Variant chr8-133258305-T-C 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.450+61A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 1,520,300 control chromosomes in the GnomAD database, including 59,636 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 6922 hom., cov: 32)

Exomes 𝑓: 0.27 ( 52714 hom. )

Consequence

NDRG1
NM_006096.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.187

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 8-133258305-T-C is Benign according to our data. Variant chr8-133258305-T-C is described in ClinVar as [Benign]. Clinvar id is 670539.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDRG1	NM_006096.4 link	c.450+61A>G		intron_variant		ENST00000323851.13	NP_006087.2	Q92597-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDRG1	ENST00000323851.13 link	c.450+61A>G		intron_variant		1	NM_006096.4	ENSP00000319977.8		Q92597-1

Frequencies

GnomAD3 genomes

AF:

0.295

AC:

44785

AN:

151964

Hom.:

6908

Cov.:

show subpopulations

Gnomad AFR

AF:

0.352

Gnomad AMI

AF:

0.465

Gnomad AMR

AF:

0.313

Gnomad ASJ

AF:

0.322

Gnomad EAS

AF:

0.0598

Gnomad SAS

AF:

0.262

Gnomad FIN

AF:

0.217

Gnomad MID

AF:

0.342

Gnomad NFE

AF:

0.284

Gnomad OTH

AF:

0.304

GnomAD4 exome

AF:

0.273

AC:

373725

AN:

1368218

Hom.:

52714

AF XY:

0.273

AC XY:

185015

AN XY:

678654

show subpopulations

Gnomad4 AFR exome

AF:

0.361

Gnomad4 AMR exome

AF:

0.298

Gnomad4 ASJ exome

AF:

0.327

Gnomad4 EAS exome

AF:

0.0752

Gnomad4 SAS exome

AF:

0.271

Gnomad4 FIN exome

AF:

0.223

Gnomad4 NFE exome

AF:

0.278

Gnomad4 OTH exome

AF:

0.273

GnomAD4 genome

AF:

0.295

AC:

44843

AN:

152082

Hom.:

6922

Cov.:

AF XY:

0.290

AC XY:

21588

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.352

Gnomad4 AMR

AF:

0.313

Gnomad4 ASJ

AF:

0.322

Gnomad4 EAS

AF:

0.0596

Gnomad4 SAS

AF:

0.263

Gnomad4 FIN

AF:

0.217

Gnomad4 NFE

AF:

0.284

Gnomad4 OTH

AF:

0.301

Alfa

AF:

0.287

Hom.:

10660

Bravo

AF:

0.304

Asia WGS

AF:

0.188

AC:

657

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Charcot-Marie-Tooth disease type 4D

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

6.3

DANN

Benign

0.75

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

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