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

Variant summary

Our verdict is Benign. The variant received -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

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

achromatopsia
Inheritance: AR Classification: LIMITED Submitted by: G2P

NDRG4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378332.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein
NDRG4	NM_001378332.1	c.178-960A>C	intron	N/A	NP_001365261.1
NDRG4	NM_001378333.1	c.178-3716A>C	intron	N/A	NP_001365262.1
NDRG4	NM_001378334.1	c.178-960A>C	intron	N/A	NP_001365263.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NDRG4	ENST00000394282.8	TSL:1	c.178-3770A>C	intron	N/A	ENSP00000377823.4	Q9ULP0-6
NDRG4	ENST00000258187.9	TSL:1	c.118-3770A>C	intron	N/A	ENSP00000258187.5	Q9ULP0-3
NDRG4	ENST00000394279.6	TSL:5	c.118-3770A>C	intron	N/A	ENSP00000377820.2	Q9ULP0-3

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

African (AFR)

AF:

0.972

AC:

25199

AN:

25928

American (AMR)

AF:

0.979

AC:

21417

AN:

21884

Ashkenazi Jewish (ASJ)

AF:

0.983

AC:

17987

AN:

18298

East Asian (EAS)

AF:

0.835

AC:

27193

AN:

32576

South Asian (SAS)

AF:

0.965

AC:

59343

AN:

61526

European-Finnish (FIN)

AF:

0.965

AC:

27607

AN:

28618

Middle Eastern (MID)

AF:

0.974

AC:

3569

AN:

3664

European-Non Finnish (NFE)

AF:

0.950

AC:

886737

AN:

933876

Other (OTH)

AF:

0.950

AC:

46944

AN:

49438

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

2619

5238

7857

10476

13095

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18584

37168

55752

74336

92920

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.955

AC:

145411

AN:

152228

Hom.:

69518

Cov.:

AF XY:

0.956

AC XY:

71162

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.967

AC:

40195

AN:

41556

American (AMR)

AF:

0.973

AC:

14892

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.983

AC:

3412

AN:

3470

East Asian (EAS)

AF:

0.831

AC:

4261

AN:

5130

South Asian (SAS)

AF:

0.963

AC:

4644

AN:

4820

European-Finnish (FIN)

AF:

0.971

AC:

10315

AN:

10620

Middle Eastern (MID)

AF:

0.959

AC:

282

AN:

294

European-Non Finnish (NFE)

AF:

0.948

AC:

64495

AN:

68004

Other (OTH)

AF:

0.958

AC:

2026

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

335

670

1005

1340

1675

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

910

1820

2730

3640

4550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.949

Hom.:

40542

Bravo

AF:

0.956

Asia WGS

AF:

0.918

AC:

3195

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

(source)

DANN

Benign

0.67

PhyloP100

0.16

PromoterAI

0.17

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over