chr8-133251811-G-T

Variant names:

• chr8-133251811-G-T
• rs7018287
• NM_006096.4:c.595-1268C>A

Variant summary

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

The NM_001374844.1(NDRG1):​c.646-1268C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,178 control chromosomes in the GnomAD database, including 3,159 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 0.19 (3159 hom., cov: 32)
• Consequence: NDRG1 NM_001374844.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00600
• Publications: 3 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: Orphanet, Labcorp Genetics (formerly Invitae), Illumina

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001374844.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDRG1	NM_006096.4	MANE Select	c.595-1268C>A		intron	N/A	NP_006087.2
	NDRG1	NM_001374844.1		c.646-1268C>A		intron	N/A	NP_001361773.1
	NDRG1	NM_001135242.2		c.595-1268C>A		intron	N/A	NP_001128714.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDRG1	ENST00000323851.13	TSL:1 MANE Select	c.595-1268C>A		intron	N/A	ENSP00000319977.8
	NDRG1	ENST00000522476.5	TSL:1	c.397-1268C>A		intron	N/A	ENSP00000427894.1
	NDRG1	ENST00000414097.6	TSL:2	c.595-1268C>A		intron	N/A	ENSP00000404854.2

Frequencies

GnomAD3 genomes AF: 0.191 AC: 28996 AN: 152060 Hom.: 3153 Cov.: 32

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.0560

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.185

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

GnomAD4 genome AF: 0.191 AC: 29031 AN: 152178 Hom.: 3159 Cov.: 32 AF XY: 0.190 AC XY: 14110 AN XY: 74408

African (AFR) AF: 0.287 AC: 11919 AN: 41478

American (AMR) AF: 0.214 AC: 3272 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 598 AN: 3472

East Asian (EAS) AF: 0.0556 AC: 288 AN: 5184

South Asian (SAS) AF: 0.147 AC: 711 AN: 4824

European-Finnish (FIN) AF: 0.120 AC: 1273 AN: 10594

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.150 AC: 10219 AN: 68014

Other (OTH) AF: 0.184 AC: 389 AN: 2116

Alfa AF: 0.164 Hom.: 3553

Bravo AF: 0.202

Asia WGS AF: 0.125 AC: 435 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.9
DANN	Benign	0.78
PhyloP100		-0.0060
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: rs7018287; hg19: chr8-134264054;