16-58494832-T-TA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000394282.8(NDRG4):c.133-117dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 531,574 control chromosomes in the GnomAD database, including 159 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.020 (105 hom., cov: 0)
  • Exomes 𝑓: 0.19 (54 hom.)
• Consequence: NDRG4 ENST00000394282.8 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.525

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 -10 ACMG points.

• BP6: Variant 16-58494832-T-TA is Benign according to our data. Variant chr16-58494832-T-TA is described in ClinVar as [Benign]. Clinvar id is 1276866.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0599 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDRG4	NM_001130487.2	c.133-117dup		intron_variant
NDRG4	NM_001363869.2	c.-281-117dup		intron_variant
NDRG4	NM_001378332.1	c.133-117dup		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDRG4	ENST00000258187.9	c.73-117dup		intron_variant		1
NDRG4	ENST00000394282.8	c.133-117dup		intron_variant		1
NDRG4	ENST00000394279.6	c.73-117dup		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0197 AC: 2663 AN: 135008 Hom.: 103 Cov.: 0

Gnomad AFR AF: 0.0620

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0108

Gnomad ASJ AF: 0.00181

Gnomad EAS AF: 0.00150

Gnomad SAS AF: 0.00148

Gnomad FIN AF: 0.00724

Gnomad MID AF: 0.00352

Gnomad NFE AF: 0.00272

Gnomad OTH AF: 0.0161

GnomAD4 exome AF: 0.187 AC: 74246 AN: 396588 Hom.: 54 AF XY: 0.186 AC XY: 38614 AN XY: 207430

Gnomad4 AFR exome AF: 0.234

Gnomad4 AMR exome AF: 0.226

Gnomad4 ASJ exome AF: 0.180

Gnomad4 EAS exome AF: 0.187

Gnomad4 SAS exome AF: 0.174

Gnomad4 FIN exome AF: 0.175

Gnomad4 NFE exome AF: 0.186

Gnomad4 OTH exome AF: 0.191

GnomAD4 genome AF: 0.0198 AC: 2673 AN: 134986 Hom.: 105 Cov.: 0 AF XY: 0.0202 AC XY: 1299 AN XY: 64370

Gnomad4 AFR AF: 0.0620

Gnomad4 AMR AF: 0.0111

Gnomad4 ASJ AF: 0.00181

Gnomad4 EAS AF: 0.00150

Gnomad4 SAS AF: 0.00149

Gnomad4 FIN AF: 0.00724

Gnomad4 NFE AF: 0.00272

Gnomad4 OTH AF: 0.0166

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

Oct 22, 2019

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs59711785; hg19: chr16-58528736;