16-58494908-G-A

Position:

• chr16-58494908-G-A

Variant summary

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

The ENST00000394282.8(NDRG4):​c.133-56G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 1,529,950 control chromosomes in the GnomAD database, including 35,408 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (2430 hom., cov: 31)
  • Exomes 𝑓: 0.21 (32978 hom.)
• Consequence: NDRG4 ENST00000394282.8 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.41

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=-0.84).
• BP6: Variant 16-58494908-G-A is Benign according to our data. Variant chr16-58494908-G-A is described in ClinVar as [Benign]. Clinvar id is 1175677.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDRG4	NM_001130487.2	c.133-56G>A		intron_variant
NDRG4	NM_001363869.2	c.-281-56G>A		intron_variant
NDRG4	NM_001378332.1	c.133-56G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDRG4	ENST00000258187.9	c.73-56G>A		intron_variant		1
NDRG4	ENST00000394282.8	c.133-56G>A		intron_variant		1
NDRG4	ENST00000394279.6	c.73-56G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23748 AN: 151836 Hom.: 2432 Cov.: 31

Gnomad AFR AF: 0.0395

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.205

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.155

GnomAD4 exome AF: 0.211 AC: 291338 AN: 1378018 Hom.: 32978 AF XY: 0.216 AC XY: 148769 AN XY: 688866

Gnomad4 AFR exome AF: 0.0320

Gnomad4 AMR exome AF: 0.0893

Gnomad4 ASJ exome AF: 0.269

Gnomad4 EAS exome AF: 0.101

Gnomad4 SAS exome AF: 0.329

Gnomad4 FIN exome AF: 0.216

Gnomad4 NFE exome AF: 0.216

Gnomad4 OTH exome AF: 0.202

GnomAD4 genome AF: 0.156 AC: 23738 AN: 151932 Hom.: 2430 Cov.: 31 AF XY: 0.158 AC XY: 11752 AN XY: 74230

Gnomad4 AFR AF: 0.0394

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.265

Gnomad4 EAS AF: 0.106

Gnomad4 SAS AF: 0.320

Gnomad4 FIN AF: 0.217

Gnomad4 NFE AF: 0.215

Gnomad4 OTH AF: 0.154

Alfa AF: 0.189 Hom.: 615

Bravo AF: 0.137

Asia WGS AF: 0.195 AC: 677 AN: 3476

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.40
DANN	Benign	0.57

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs34720527; hg19: chr16-58528812;