chr8-133285700-G-C

Variant names:

• chr8-133285700-G-C
• rs2930002
• NM_006096.4:c.-18-1371C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006096.4(NDRG1):​c.-18-1371C>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 152,170 control chromosomes in the GnomAD database, including 6,249 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.27 (6249 hom., cov: 33)
• Consequence: NDRG1 NM_006096.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0640
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• Charcot-Marie-Tooth disease type 4D

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Illumina, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006096.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDRG1	NM_006096.4	MANE Select	c.-18-1371C>G		intron	N/A	NP_006087.2
	NDRG1	NM_001374844.1		c.-18-1371C>G		intron	N/A	NP_001361773.1
	NDRG1	NM_001135242.2		c.-18-1371C>G		intron	N/A	NP_001128714.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDRG1	ENST00000323851.13	TSL:1 MANE Select	c.-18-1371C>G		intron	N/A	ENSP00000319977.8
	NDRG1	ENST00000522476.5	TSL:1	c.-100+11434C>G		intron	N/A	ENSP00000427894.1
	NDRG1	ENST00000414097.6	TSL:2	c.-18-1371C>G		intron	N/A	ENSP00000404854.2

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41753 AN: 152052 Hom.: 6242 Cov.: 33

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.494

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.287

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.275 AC: 41790 AN: 152170 Hom.: 6249 Cov.: 33 AF XY: 0.278 AC XY: 20661 AN XY: 74372

African (AFR) AF: 0.165 AC: 6866 AN: 41532

American (AMR) AF: 0.266 AC: 4067 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.311 AC: 1081 AN: 3472

East Asian (EAS) AF: 0.494 AC: 2549 AN: 5160

South Asian (SAS) AF: 0.334 AC: 1612 AN: 4826

European-Finnish (FIN) AF: 0.361 AC: 3817 AN: 10584

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.307 AC: 20898 AN: 67996

Other (OTH) AF: 0.287 AC: 606 AN: 2114

Alfa AF: 0.303 Hom.: 908

Bravo AF: 0.264

Asia WGS AF: 0.439 AC: 1527 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	15
DANN	Benign	0.75
PhyloP100		0.064
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2930002; hg19: chr8-134297943;