Genetic Variant NDRG4:c.132+10A>G (chr16-58487860-A-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2

The NM_001378332.1(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
NM_001378332.1 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0200

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 -14 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_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
NDRG4	NM_001378332.1 link	c.132+10A>G	intron_variant	Intron 2 of 17	NP_001365261.1
NDRG4	NM_001378333.1 link	c.132+10A>G	intron_variant	Intron 2 of 16	NP_001365262.1
NDRG4	NM_001378334.1 link	c.132+10A>G	intron_variant	Intron 2 of 16	NP_001365263.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
NDRG4	ENST00000394282.8 link	c.132+10A>G	intron_variant	Intron 2 of 15	1	ENSP00000377823.4	Q9ULP0-6
NDRG4	ENST00000258187.9 link	c.72+10A>G	intron_variant	Intron 2 of 15	1	ENSP00000258187.5	Q9ULP0-3
NDRG4	ENST00000394279.6 link	c.72+10A>G	intron_variant	Intron 2 of 15	5	ENSP00000377820.2	Q9ULP0-3

Frequencies

GnomAD3 genomes

AF:

0.00749

AC:

1140

AN:

152126

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00814

AC XY:

589

AN XY:

72374

show subpopulations

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.:

AF XY:

0.0112

AC XY:

7598

AN XY:

676496

show subpopulations

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.:

Cov.:

AF XY:

0.00717

AC XY:

534

AN XY:

74438

show subpopulations

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.:

Bravo

AF:

0.00693

Asia WGS

AF:

0.00635

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 29, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

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