16-58503993-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001242835.2(NDRG4):c.127+90G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 1,528,942 control chromosomes in the GnomAD database, including 150,545 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.36 (11370 hom., cov: 31)
  • Exomes 𝑓: 0.44 (139175 hom.)
• Consequence: NDRG4 NM_001242835.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.86

Genes affected

NDRG4 (HGNC:14466): (NDRG family member 4) 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 that is required for cell cycle progression and survival in primary astrocytes and may be involved in the regulation of mitogenic signalling in vascular smooth muscles cells. Alternative splicing results in multiple transcripts encoding different isoforms.[provided by RefSeq, Jun 2011]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 16-58503993-G-A is Benign according to our data. Variant chr16-58503993-G-A is described in ClinVar as [Benign]. Clinvar id is 1234462.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDRG4	NM_001242835.2	c.127+90G>A		intron_variant		ENST00000570248.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDRG4	ENST00000570248.6	c.127+90G>A		intron_variant		1	NM_001242835.2	P1

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54557 AN: 151550 Hom.: 11365 Cov.: 31

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.356

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.377

GnomAD3 exomes AF: 0.389 AC: 93137 AN: 239488 Hom.: 19602 AF XY: 0.400 AC XY: 51993 AN XY: 130116

Gnomad AFR exome AF: 0.154

Gnomad AMR exome AF: 0.259

Gnomad ASJ exome AF: 0.454

Gnomad EAS exome AF: 0.229

Gnomad SAS exome AF: 0.396

Gnomad FIN exome AF: 0.476

Gnomad NFE exome AF: 0.469

Gnomad OTH exome AF: 0.415

GnomAD4 exome AF: 0.441 AC: 607601 AN: 1377272 Hom.: 139175 Cov.: 24 AF XY: 0.441 AC XY: 303858 AN XY: 688898

Gnomad4 AFR exome AF: 0.148

Gnomad4 AMR exome AF: 0.264

Gnomad4 ASJ exome AF: 0.455

Gnomad4 EAS exome AF: 0.224

Gnomad4 SAS exome AF: 0.404

Gnomad4 FIN exome AF: 0.464

Gnomad4 NFE exome AF: 0.469

Gnomad4 OTH exome AF: 0.424

GnomAD4 genome AF: 0.360 AC: 54576 AN: 151670 Hom.: 11370 Cov.: 31 AF XY: 0.358 AC XY: 26517 AN XY: 74074

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.325

Gnomad4 ASJ AF: 0.437

Gnomad4 EAS AF: 0.232

Gnomad4 SAS AF: 0.399

Gnomad4 FIN AF: 0.488

Gnomad4 NFE AF: 0.473

Gnomad4 OTH AF: 0.374

Alfa AF: 0.425 Hom.: 3898

Bravo AF: 0.335

Asia WGS AF: 0.307 AC: 1070 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 10, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.012
Dann	Benign	0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2427787; hg19: chr16-58537897; COSMIC: COSV50748712; COSMIC: COSV50748712;