16-58510391-G-C

Position:

• chr16-58510391-G-C

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.866-254G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 152,114 control chromosomes in the GnomAD database, including 31,498 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.63 (31498 hom., cov: 33)
• Consequence: NDRG4 NM_001242835.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.11

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=-0.93).
• BP6: Variant 16-58510391-G-C is Benign according to our data. Variant chr16-58510391-G-C is described in ClinVar as [Benign]. Clinvar id is 1272101.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.932 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NDRG4	NM_001242835.2	c.866-254G>C		intron_variant		ENST00000570248.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NDRG4	ENST00000570248.6	c.866-254G>C		intron_variant		1	NM_001242835.2	P1

Frequencies

GnomAD3 genomes AF: 0.632 AC: 96029 AN: 151998 Hom.: 31453 Cov.: 33

Gnomad AFR AF: 0.747

Gnomad AMI AF: 0.381

Gnomad AMR AF: 0.670

Gnomad ASJ AF: 0.664

Gnomad EAS AF: 0.955

Gnomad SAS AF: 0.762

Gnomad FIN AF: 0.519

Gnomad MID AF: 0.685

Gnomad NFE AF: 0.538

Gnomad OTH AF: 0.616

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

GnomAD4 genome AF: 0.632 AC: 96132 AN: 152114 Hom.: 31498 Cov.: 33 AF XY: 0.637 AC XY: 47364 AN XY: 74356

Gnomad4 AFR AF: 0.748

Gnomad4 AMR AF: 0.671

Gnomad4 ASJ AF: 0.664

Gnomad4 EAS AF: 0.955

Gnomad4 SAS AF: 0.762

Gnomad4 FIN AF: 0.519

Gnomad4 NFE AF: 0.538

Gnomad4 OTH AF: 0.622

Alfa AF: 0.596 Hom.: 3469

Bravo AF: 0.646

Asia WGS AF: 0.840 AC: 2922 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	-0.93
CADD	Benign	1.0
DANN	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs246192; hg19: chr16-58544295;