chr8-133251811-G-T

Position:

• chr8-133251811-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006096.4(NDRG1):​c.595-1268C>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_006096.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00600

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDRG1	NM_006096.4	c.595-1268C>A		intron_variant		ENST00000323851.13	NP_006087.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDRG1	ENST00000323851.13	c.595-1268C>A		intron_variant		1	NM_006096.4	ENSP00000319977	P1

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

Gnomad4 AFR AF: 0.287

Gnomad4 AMR AF: 0.214

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.0556

Gnomad4 SAS AF: 0.147

Gnomad4 FIN AF: 0.120

Gnomad4 NFE AF: 0.150

Gnomad4 OTH AF: 0.184

Alfa AF: 0.159 Hom.: 2598

Bravo AF: 0.202

Asia WGS AF: 0.125 AC: 435 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.9
DANN	Benign	0.78

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: rs7018287; hg19: chr8-134264054;