chr8-133238187-C-T

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

2

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]

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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
NDRG1NM_006096.4 linkuse as main transcriptc.*691G>A 3_prime_UTR_variant 16/16 ENST00000323851.13

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NDRG1ENST00000323851.13 linkuse as main transcriptc.*691G>A 3_prime_UTR_variant 16/161 NM_006096.4 P1Q92597-1

Frequencies

GnomAD3 genomes
AF:
0.321
AC:
48777
AN:
151906
Hom.:
8115
Cov.:
32
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.:
0
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.:
32
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 submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Charcot-Marie-Tooth disease type 4D Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This 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.

Other links and lift over

dbSNP: rs1049694; hg19: chr8-134250430; API