Variant 8-133238187-C-T 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.*691G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 232,512 control chromosomes in the GnomAD database, including 12,228 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 8123 hom., cov: 32)

Exomes 𝑓: 0.30 ( 4105 hom. )

Consequence

NDRG1
NM_006096.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.716

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=-0.88).

BP6

Variant 8-133238187-C-T is Benign according to our data. Variant chr8-133238187-C-T is described in ClinVar as [Benign]. Clinvar id is 362019.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDRG1	NM_006096.4 linkuse as main transcript	c.*691G>A		3_prime_UTR_variant	16/16	ENST00000323851.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDRG1	ENST00000323851.13 linkuse as main transcript	c.*691G>A		3_prime_UTR_variant	16/16	1	NM_006096.4	P1	Q92597-1

Frequencies

GnomAD3 genomes

AF:

0.321

AC:

48777

AN:

151906

Hom.:

8115

Cov.:

show subpopulations

Gnomad AFR

AF:

0.305

Gnomad AMI

AF:

0.513

Gnomad AMR

AF:

0.360

Gnomad ASJ

AF:

0.382

Gnomad EAS

AF:

0.0545

Gnomad SAS

AF:

0.248

Gnomad FIN

AF:

0.302

Gnomad MID

AF:

0.326

Gnomad NFE

AF:

0.344

Gnomad OTH

AF:

0.328

GnomAD4 exome

AF:

0.305

AC:

24547

AN:

80488

Hom.:

4105

Cov.:

AF XY:

0.308

AC XY:

11383

AN XY:

37000

show subpopulations

Gnomad4 AFR exome

AF:

0.304

Gnomad4 AMR exome

AF:

0.350

Gnomad4 ASJ exome

AF:

0.398

Gnomad4 EAS exome

AF:

0.0703

Gnomad4 SAS exome

AF:

0.246

Gnomad4 FIN exome

AF:

0.362

Gnomad4 NFE exome

AF:

0.345

Gnomad4 OTH exome

AF:

0.325

GnomAD4 genome

AF:

0.321

AC:

48822

AN:

152024

Hom.:

8123

Cov.:

AF XY:

0.318

AC XY:

23596

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.306

Gnomad4 AMR

AF:

0.360

Gnomad4 ASJ

AF:

0.382

Gnomad4 EAS

AF:

0.0541

Gnomad4 SAS

AF:

0.249

Gnomad4 FIN

AF:

0.302

Gnomad4 NFE

AF:

0.345

Gnomad4 OTH

AF:

0.326

Alfa

AF:

0.337

Hom.:

3594

Bravo

AF:

0.327

Asia WGS

AF:

0.161

AC:

565

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

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

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.25

DANN

Benign

0.52

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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