16-58494832-T-TAA

Position:

• chr16-58494832-T-TAA

Variant summary

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

The ENST00000394282.8(NDRG4):​c.133-118_133-117dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 532,952 control chromosomes in the GnomAD database, including 38,041 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.74 (37276 hom., cov: 0)
  • Exomes 𝑓: 0.36 (765 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-TAA is Benign according to our data. Variant chr16-58494832-T-TAA is described in ClinVar as [Benign]. Clinvar id is 1290213.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDRG4	NM_001130487.2	c.133-118_133-117dup		intron_variant
NDRG4	NM_001363869.2	c.-281-118_-281-117dup		intron_variant
NDRG4	NM_001378332.1	c.133-118_133-117dup		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDRG4	ENST00000258187.9	c.73-118_73-117dup		intron_variant		1
NDRG4	ENST00000394282.8	c.133-118_133-117dup		intron_variant		1
NDRG4	ENST00000394279.6	c.73-118_73-117dup		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.744 AC: 100283 AN: 134750 Hom.: 37281 Cov.: 0

Gnomad AFR AF: 0.777

Gnomad AMI AF: 0.782

Gnomad AMR AF: 0.835

Gnomad ASJ AF: 0.712

Gnomad EAS AF: 0.713

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.701

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.721

Gnomad OTH AF: 0.759

GnomAD4 exome AF: 0.356 AC: 141665 AN: 398226 Hom.: 765 AF XY: 0.354 AC XY: 73682 AN XY: 208066

Gnomad4 AFR exome AF: 0.393

Gnomad4 AMR exome AF: 0.408

Gnomad4 ASJ exome AF: 0.350

Gnomad4 EAS exome AF: 0.370

Gnomad4 SAS exome AF: 0.297

Gnomad4 FIN exome AF: 0.357

Gnomad4 NFE exome AF: 0.357

Gnomad4 OTH exome AF: 0.363

GnomAD4 genome AF: 0.744 AC: 100265 AN: 134726 Hom.: 37276 Cov.: 0 AF XY: 0.742 AC XY: 47675 AN XY: 64216

Gnomad4 AFR AF: 0.777

Gnomad4 AMR AF: 0.834

Gnomad4 ASJ AF: 0.712

Gnomad4 EAS AF: 0.713

Gnomad4 SAS AF: 0.636

Gnomad4 FIN AF: 0.701

Gnomad4 NFE AF: 0.721

Gnomad4 OTH AF: 0.757

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

Aug 21, 2019

- -

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;