rs2977499

Variant names:

• chr8-133267532-T-C
• rs2977499
• NM_006096.4:c.100-2880A>G

Your query was ambiguous. Multiple possible variants found:

• chr8-133267532-T-C
• chr8-133267532-T-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.100-2880A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 152,084 control chromosomes in the GnomAD database, including 5,548 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 0.26 (5548 hom., cov: 32)
• Consequence: NDRG1 NM_006096.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.14
• Publications: 1 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=-0.49).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDRG1	NM_006096.4	c.100-2880A>G		intron_variant	Intron 3 of 15	ENST00000323851.13	NP_006087.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDRG1	ENST00000323851.13	c.100-2880A>G		intron_variant	Intron 3 of 15	1	NM_006096.4	ENSP00000319977.8

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39227 AN: 151966 Hom.: 5547 Cov.: 32

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.263

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

GnomAD4 genome AF: 0.258 AC: 39247 AN: 152084 Hom.: 5548 Cov.: 32 AF XY: 0.261 AC XY: 19405 AN XY: 74344

African (AFR) AF: 0.147 AC: 6082 AN: 41504

American (AMR) AF: 0.326 AC: 4993 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 981 AN: 3468

East Asian (EAS) AF: 0.420 AC: 2161 AN: 5150

South Asian (SAS) AF: 0.278 AC: 1339 AN: 4820

European-Finnish (FIN) AF: 0.314 AC: 3329 AN: 10588

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.286 AC: 19439 AN: 67948

Other (OTH) AF: 0.262 AC: 553 AN: 2108

Alfa AF: 0.282 Hom.: 2094

Bravo AF: 0.256

Asia WGS AF: 0.359 AC: 1245 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	21
DANN	Benign	0.85
PhyloP100		2.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs2977499; hg19: chr8-134279775;