chr8-133237256-A-C
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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
NM_006096.4 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.94
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 |
---|---|---|---|---|---|---|---|
NDRG1 | NM_006096.4 | c.*1622T>G | 3_prime_UTR_variant | 16/16 | ENST00000323851.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NDRG1 | ENST00000323851.13 | c.*1622T>G | 3_prime_UTR_variant | 16/16 | 1 | NM_006096.4 | P1 | ||
ENST00000688585.1 | n.672T>G | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes AF: 0.0276 AC: 4193AN: 152164Hom.: 159 Cov.: 32
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GnomAD4 exome AF: 0.00675 AC: 522AN: 77316Hom.: 24 Cov.: 0 AF XY: 0.00570 AC XY: 203AN XY: 35596
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GnomAD4 genome AF: 0.0276 AC: 4206AN: 152282Hom.: 158 Cov.: 32 AF XY: 0.0265 AC XY: 1976AN XY: 74460
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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 submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This 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
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at