16-58487860-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The ENST00000394282.8(NDRG4):c.132+10A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0109 in 1,528,474 control chromosomes in the GnomAD database, including 123 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0075 (9 hom., cov: 32)
  • Exomes 𝑓: 0.011 (114 hom.)
• Consequence: NDRG4 ENST00000394282.8 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0200

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 16-58487860-A-G is Benign according to our data. Variant chr16-58487860-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1316367.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDRG4	NM_001130487.2	c.132+10A>G		intron_variant
NDRG4	NM_001363869.2	c.-282+10A>G		intron_variant
NDRG4	NM_001378332.1	c.132+10A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDRG4	ENST00000258187.9	c.72+10A>G		intron_variant		1
NDRG4	ENST00000394282.8	c.132+10A>G		intron_variant		1
NDRG4	ENST00000394279.6	c.72+10A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.00749 AC: 1140 AN: 152126 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.00224

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00425

Gnomad ASJ AF: 0.00922

Gnomad EAS AF: 0.000967

Gnomad SAS AF: 0.00498

Gnomad FIN AF: 0.00800

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0120

Gnomad OTH AF: 0.00813

GnomAD3 exomes AF: 0.00773 AC: 1048 AN: 135616 Hom.: 4 AF XY: 0.00814 AC XY: 589 AN XY: 72374

Gnomad AFR exome AF: 0.00135

Gnomad AMR exome AF: 0.00277

Gnomad ASJ exome AF: 0.0119

Gnomad EAS exome AF: 0.000202

Gnomad SAS exome AF: 0.00650

Gnomad FIN exome AF: 0.00770

Gnomad NFE exome AF: 0.0122

Gnomad OTH exome AF: 0.00783

GnomAD4 exome AF: 0.0113 AC: 15495 AN: 1376230 Hom.: 114 Cov.: 30 AF XY: 0.0112 AC XY: 7598 AN XY: 676496

Gnomad4 AFR exome AF: 0.00146

Gnomad4 AMR exome AF: 0.00326

Gnomad4 ASJ exome AF: 0.00936

Gnomad4 EAS exome AF: 0.0000860

Gnomad4 SAS exome AF: 0.00739

Gnomad4 FIN exome AF: 0.00960

Gnomad4 NFE exome AF: 0.0126

Gnomad4 OTH exome AF: 0.0104

GnomAD4 genome AF: 0.00748 AC: 1139 AN: 152244 Hom.: 9 Cov.: 32 AF XY: 0.00717 AC XY: 534 AN XY: 74438

Gnomad4 AFR AF: 0.00224

Gnomad4 AMR AF: 0.00425

Gnomad4 ASJ AF: 0.00922

Gnomad4 EAS AF: 0.000969

Gnomad4 SAS AF: 0.00498

Gnomad4 FIN AF: 0.00800

Gnomad4 NFE AF: 0.0120

Gnomad4 OTH AF: 0.00805

Alfa AF: 0.0106 Hom.: 2

Bravo AF: 0.00693

Asia WGS AF: 0.00635 AC: 22 AN: 3478

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

Nov 29, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
Cadd	Benign	9.5
Dann	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs374638909; hg19: chr16-58521764;