chr8-133237256-A-C

Variant summary

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

The NM_006096.4(NDRG1):​c.*1622T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0206 in 229,598 control chromosomes in the GnomAD database, including 182 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.028 ( 158 hom., cov: 32)
Exomes 𝑓: 0.0068 ( 24 hom. )

Consequence

NDRG1
NM_006096.4 3_prime_UTR

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.94
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=-0.77).
BP6
Variant 8-133237256-A-C is Benign according to our data. Variant chr8-133237256-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 362008.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0909 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NDRG1NM_006096.4 linkuse as main transcriptc.*1622T>G 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.*1622T>G 3_prime_UTR_variant 16/161 NM_006096.4 P1Q92597-1
ENST00000688585.1 linkuse as main transcriptn.672T>G non_coding_transcript_exon_variant 1/1

Frequencies

GnomAD3 genomes
AF:
0.0276
AC:
4193
AN:
152164
Hom.:
159
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0933
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0144
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00186
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0127
Gnomad NFE
AF:
0.000573
Gnomad OTH
AF:
0.0278
GnomAD4 exome
AF:
0.00675
AC:
522
AN:
77316
Hom.:
24
Cov.:
0
AF XY:
0.00570
AC XY:
203
AN XY:
35596
show subpopulations
Gnomad4 AFR exome
AF:
0.102
Gnomad4 AMR exome
AF:
0.0161
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000817
Gnomad4 OTH exome
AF:
0.0106
GnomAD4 genome
AF:
0.0276
AC:
4206
AN:
152282
Hom.:
158
Cov.:
32
AF XY:
0.0265
AC XY:
1976
AN XY:
74460
show subpopulations
Gnomad4 AFR
AF:
0.0934
Gnomad4 AMR
AF:
0.0144
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00145
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000559
Gnomad4 OTH
AF:
0.0275
Alfa
AF:
0.0132
Hom.:
19
Bravo
AF:
0.0318
Asia WGS
AF:
0.00549
AC:
19
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Charcot-Marie-Tooth disease type 4D Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaApr 27, 2017This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.77
CADD
Benign
6.5
DANN
Benign
0.74

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: rs7825439; hg19: chr8-134249499; API