16-58487526-A-G

Variant summary

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

The ENST00000394282.8(NDRG4):c.38-230A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 152,104 control chromosomes in the GnomAD database, including 33,757 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.66 (33757 hom., cov: 33)
• Consequence: NDRG4 ENST00000394282.8 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.630

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 16-58487526-A-G is Benign according to our data. Variant chr16-58487526-A-G is described in ClinVar as [Benign]. Clinvar id is 1261668.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDRG4	NM_001130487.2	c.38-230A>G		intron_variant
NDRG4	NM_001363869.2	c.-376-230A>G		intron_variant
NDRG4	NM_001378332.1	c.38-230A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDRG4	ENST00000258187.9	c.-23-230A>G		intron_variant		1
NDRG4	ENST00000394282.8	c.38-230A>G		intron_variant		1
NDRG4	ENST00000394279.6	c.-23-230A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.662 AC: 100683 AN: 151988 Hom.: 33731 Cov.: 33

Gnomad AFR AF: 0.577

Gnomad AMI AF: 0.701

Gnomad AMR AF: 0.634

Gnomad ASJ AF: 0.776

Gnomad EAS AF: 0.517

Gnomad SAS AF: 0.761

Gnomad FIN AF: 0.672

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.717

Gnomad OTH AF: 0.672

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.662 AC: 100757 AN: 152104 Hom.: 33757 Cov.: 33 AF XY: 0.662 AC XY: 49213 AN XY: 74332

Gnomad4 AFR AF: 0.577

Gnomad4 AMR AF: 0.634

Gnomad4 ASJ AF: 0.776

Gnomad4 EAS AF: 0.518

Gnomad4 SAS AF: 0.761

Gnomad4 FIN AF: 0.672

Gnomad4 NFE AF: 0.717

Gnomad4 OTH AF: 0.676

Alfa AF: 0.684 Hom.: 5290

Bravo AF: 0.653

Asia WGS AF: 0.649 AC: 2257 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

Aug 21, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	3.4
Dann	Benign	0.35

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8050282; hg19: chr16-58521430;