16-58464080-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000394282.8(NDRG4):c.-351G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0266 in 244,438 control chromosomes in the GnomAD database, including 138 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.030 (103 hom., cov: 32)
  • Exomes 𝑓: 0.022 (35 hom.)
• Consequence: NDRG4 ENST00000394282.8 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.02

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=-0.71).
• BP6: Variant 16-58464080-G-T is Benign according to our data. Variant chr16-58464080-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1316103.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0297 (4514/152090) while in subpopulation AFR AF= 0.0483 (2008/41536). AF 95% confidence interval is 0.0466. There are 103 homozygotes in gnomad4. There are 2160 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 102 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDRG4	NM_001378338.1	c.-24+283G>T		intron_variant
NDRG4	NM_001378339.1	c.-24+283G>T		intron_variant
NDRG4	NM_001378342.1	c.-24+283G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDRG4	ENST00000394282.8	c.-351G>T		5_prime_UTR_variant	1/16	1
NDRG4	ENST00000258187.9	c.-24+283G>T		intron_variant		1
NDRG4	ENST00000564126.5	c.-24+283G>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0296 AC: 4502 AN: 151984 Hom.: 102 Cov.: 32

Gnomad AFR AF: 0.0483

Gnomad AMI AF: 0.00879

Gnomad AMR AF: 0.0164

Gnomad ASJ AF: 0.0300

Gnomad EAS AF: 0.0402

Gnomad SAS AF: 0.0459

Gnomad FIN AF: 0.0103

Gnomad MID AF: 0.0541

Gnomad NFE AF: 0.0225

Gnomad OTH AF: 0.0254

GnomAD4 exome AF: 0.0216 AC: 1993 AN: 92348 Hom.: 35 Cov.: 0 AF XY: 0.0208 AC XY: 975 AN XY: 46788

Gnomad4 AFR exome AF: 0.0411

Gnomad4 AMR exome AF: 0.0129

Gnomad4 ASJ exome AF: 0.0271

Gnomad4 EAS exome AF: 0.0223

Gnomad4 SAS exome AF: 0.0437

Gnomad4 FIN exome AF: 0.00678

Gnomad4 NFE exome AF: 0.0213

Gnomad4 OTH exome AF: 0.0246

GnomAD4 genome AF: 0.0297 AC: 4514 AN: 152090 Hom.: 103 Cov.: 32 AF XY: 0.0290 AC XY: 2160 AN XY: 74378

Gnomad4 AFR AF: 0.0483

Gnomad4 AMR AF: 0.0164

Gnomad4 ASJ AF: 0.0300

Gnomad4 EAS AF: 0.0401

Gnomad4 SAS AF: 0.0462

Gnomad4 FIN AF: 0.0103

Gnomad4 NFE AF: 0.0225

Gnomad4 OTH AF: 0.0285

Alfa AF: 0.0241 Hom.: 10

Bravo AF: 0.0292

Asia WGS AF: 0.0340 AC: 118 AN: 3474

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 16, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	3.7
Dann	Benign	0.96

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs111484016; hg19: chr16-58497984;