8-133285700-G-C

Position:

• chr8-133285700-G-C

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDRG1	NM_006096.4	c.-18-1371C>G		intron_variant		ENST00000323851.13	NP_006087.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDRG1	ENST00000323851.13	c.-18-1371C>G		intron_variant		1	NM_006096.4	ENSP00000319977.8

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

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.266

Gnomad4 ASJ AF: 0.311

Gnomad4 EAS AF: 0.494

Gnomad4 SAS AF: 0.334

Gnomad4 FIN AF: 0.361

Gnomad4 NFE AF: 0.307

Gnomad4 OTH AF: 0.287

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	15
DANN	Benign	0.75

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

Other links and lift over

dbSNP: rs2930002; hg19: chr8-134297943;