Genetic Variant NDRG4:c.178-3770A>C (chr16-58500028-A-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001378332.1(NDRG4):c.178-960A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.95 in 1,328,036 control chromosomes in the GnomAD database, including 599,406 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.96 ( 69518 hom., cov: 32)

Exomes 𝑓: 0.95 ( 529888 hom. )

Consequence

NDRG4
NM_001378332.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.164

Variant links:

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]

NDRG4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 16-58500028-A-C is Benign according to our data. Variant chr16-58500028-A-C is described in ClinVar as [Benign]. Clinvar id is 1267331.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.96 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDRG4	NM_001242835.2 link	c.-221A>C		upstream_gene_variant		ENST00000570248.6	NP_001229764.1	Q9ULP0-1A0A0S2Z5R7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDRG4	ENST00000570248.6 link	c.-221A>C		upstream_gene_variant		1	NM_001242835.2	ENSP00000457659.1		Q9ULP0-1

Frequencies

GnomAD3 genomes

AF:

0.955

AC:

145293

AN:

152110

Hom.:

69460

Cov.:

show subpopulations

Gnomad AFR

AF:

0.967

Gnomad AMI

AF:

0.975

Gnomad AMR

AF:

0.973

Gnomad ASJ

AF:

0.983

Gnomad EAS

AF:

0.830

Gnomad SAS

AF:

0.963

Gnomad FIN

AF:

0.971

Gnomad MID

AF:

0.962

Gnomad NFE

AF:

0.948

Gnomad OTH

AF:

0.959

GnomAD4 exome

AF:

0.949

AC:

1115996

AN:

1175808

Hom.:

529888

Cov.:

AF XY:

0.949

AC XY:

545369

AN XY:

574446

show subpopulations

Gnomad4 AFR exome

AF:

0.972

Gnomad4 AMR exome

AF:

0.979

Gnomad4 ASJ exome

AF:

0.983

Gnomad4 EAS exome

AF:

0.835

Gnomad4 SAS exome

AF:

0.965

Gnomad4 FIN exome

AF:

0.965

Gnomad4 NFE exome

AF:

0.950

Gnomad4 OTH exome

AF:

0.950

GnomAD4 genome

AF:

0.955

AC:

145411

AN:

152228

Hom.:

69518

Cov.:

AF XY:

0.956

AC XY:

71162

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.967

Gnomad4 AMR

AF:

0.973

Gnomad4 ASJ

AF:

0.983

Gnomad4 EAS

AF:

0.831

Gnomad4 SAS

AF:

0.963

Gnomad4 FIN

AF:

0.971

Gnomad4 NFE

AF:

0.948

Gnomad4 OTH

AF:

0.958

Alfa

AF:

0.952

Hom.:

15993

Bravo

AF:

0.956

Asia WGS

AF:

0.918

AC:

3195

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 10, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

DANN

Benign

0.67

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over