16-58499805-G-T

Variant summary

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

The ENST00000394282.8(NDRG4):c.178-3993G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.668 in 303,678 control chromosomes in the GnomAD database, including 68,567 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.66 (33360 hom., cov: 35)
  • Exomes 𝑓: 0.68 (35207 hom.)
• Consequence: NDRG4 ENST00000394282.8 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0570

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=-0.82).
• BP6: Variant 16-58499805-G-T is Benign according to our data. Variant chr16-58499805-G-T is described in ClinVar as [Benign]. Clinvar id is 1236404.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDRG4	NM_001130487.2	c.178-3993G>T		intron_variant
NDRG4	NM_001363869.2	c.-236-3901G>T		intron_variant
NDRG4	NM_001378332.1	c.178-1183G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDRG4	ENST00000258187.9	c.118-3993G>T		intron_variant		1
NDRG4	ENST00000394282.8	c.178-3993G>T		intron_variant		1
NDRG4	ENST00000394279.6	c.118-3993G>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.660 AC: 100388 AN: 152070 Hom.: 33334 Cov.: 35

Gnomad AFR AF: 0.643

Gnomad AMI AF: 0.622

Gnomad AMR AF: 0.698

Gnomad ASJ AF: 0.708

Gnomad EAS AF: 0.777

Gnomad SAS AF: 0.775

Gnomad FIN AF: 0.705

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.637

Gnomad OTH AF: 0.636

GnomAD4 exome AF: 0.676 AC: 102380 AN: 151490 Hom.: 35207 Cov.: 0 AF XY: 0.686 AC XY: 56306 AN XY: 82044

Gnomad4 AFR exome AF: 0.622

Gnomad4 AMR exome AF: 0.758

Gnomad4 ASJ exome AF: 0.692

Gnomad4 EAS exome AF: 0.782

Gnomad4 SAS exome AF: 0.765

Gnomad4 FIN exome AF: 0.691

Gnomad4 NFE exome AF: 0.637

Gnomad4 OTH exome AF: 0.664

GnomAD4 genome AF: 0.660 AC: 100463 AN: 152188 Hom.: 33360 Cov.: 35 AF XY: 0.668 AC XY: 49731 AN XY: 74394

Gnomad4 AFR AF: 0.642

Gnomad4 AMR AF: 0.699

Gnomad4 ASJ AF: 0.708

Gnomad4 EAS AF: 0.777

Gnomad4 SAS AF: 0.775

Gnomad4 FIN AF: 0.705

Gnomad4 NFE AF: 0.637

Gnomad4 OTH AF: 0.639

Alfa AF: 0.644 Hom.: 58644

Bravo AF: 0.656

Asia WGS AF: 0.774 AC: 2692 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

Apr 09, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	11
Dann	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2432560; hg19: chr16-58533709;