rs40186

chr16-58511164-G-A

Variant summary

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

The NM_001242835.2(NDRG4):c.905-258G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 515,904 control chromosomes in the GnomAD database, including 6,411 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.13 (1647 hom., cov: 33)
  • Exomes 𝑓: 0.15 (4764 hom.)
• Consequence: NDRG4 NM_001242835.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.34

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=-0.92).
• BP6: Variant 16-58511164-G-A is Benign according to our data. Variant chr16-58511164-G-A is described in ClinVar as [Benign]. Clinvar id is 1228881.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDRG4	NM_001242835.2	c.905-258G>A		intron_variant		ENST00000570248.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDRG4	ENST00000570248.6	c.905-258G>A		intron_variant		1	NM_001242835.2	P1

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19784 AN: 152076 Hom.: 1643 Cov.: 33

Gnomad AFR AF: 0.0362

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.0955

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.128

GnomAD4 exome AF: 0.154 AC: 55831 AN: 363710 Hom.: 4764 Cov.: 2 AF XY: 0.152 AC XY: 28634 AN XY: 188980

Gnomad4 AFR exome AF: 0.0365

Gnomad4 AMR exome AF: 0.252

Gnomad4 ASJ exome AF: 0.167

Gnomad4 EAS exome AF: 0.170

Gnomad4 SAS exome AF: 0.111

Gnomad4 FIN exome AF: 0.160

Gnomad4 NFE exome AF: 0.156

Gnomad4 OTH exome AF: 0.152

GnomAD4 genome AF: 0.130 AC: 19813 AN: 152194 Hom.: 1647 Cov.: 33 AF XY: 0.131 AC XY: 9773 AN XY: 74388

Gnomad4 AFR AF: 0.0362

Gnomad4 AMR AF: 0.238

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.183

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.152

Gnomad4 NFE AF: 0.155

Gnomad4 OTH AF: 0.135

Alfa AF: 0.157 Hom.: 2440

Bravo AF: 0.133

Asia WGS AF: 0.152 AC: 532 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

Jan 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.16
Dann	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs40186; hg19: chr16-58545068;