Genetic Variant NDRG4:c.133-132_133-131insAA (chr16-58494832-T-TAA) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001378332.1(NDRG4):c.133-118_133-117dupAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 532,952 control chromosomes in the GnomAD database, including 38,041 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.74 ( 37276 hom., cov: 0)

Exomes 𝑓: 0.36 ( 765 hom. )

Consequence

NDRG4
NM_001378332.1 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.525

Publications

0 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 -10 ACMG points.

BP6

Variant 16-58494832-T-TAA is Benign according to our data. Variant chr16-58494832-T-TAA is described in ClinVar as Benign. ClinVar VariationId is 1290213.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.821 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.133-118_133-117dupAA	intron	N/A	NP_001365261.1
NDRG4	NM_001378333.1	c.133-118_133-117dupAA	intron	N/A	NP_001365262.1
NDRG4	NM_001378334.1	c.133-118_133-117dupAA	intron	N/A	NP_001365263.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NDRG4	ENST00000394282.8	TSL:1	c.133-132_133-131insAA	intron	N/A	ENSP00000377823.4	Q9ULP0-6
NDRG4	ENST00000258187.9	TSL:1	c.73-132_73-131insAA	intron	N/A	ENSP00000258187.5	Q9ULP0-3
NDRG4	ENST00000394279.6	TSL:5	c.73-132_73-131insAA	intron	N/A	ENSP00000377820.2	Q9ULP0-3

Frequencies

GnomAD3 genomes

AF:

0.744

AC:

100283

AN:

134750

Hom.:

37281

Cov.:

show subpopulations

Gnomad AFR

AF:

0.777

Gnomad AMI

AF:

0.782

Gnomad AMR

AF:

0.835

Gnomad ASJ

AF:

0.712

Gnomad EAS

AF:

0.713

Gnomad SAS

AF:

0.636

Gnomad FIN

AF:

0.701

Gnomad MID

AF:

0.722

Gnomad NFE

AF:

0.721

Gnomad OTH

AF:

0.759

GnomAD4 exome

AF:

0.356

AC:

141665

AN:

398226

Hom.:

765

AF XY:

0.354

AC XY:

73682

AN XY:

208066

show subpopulations

African (AFR)

AF:

0.393

AC:

4202

AN:

10702

American (AMR)

AF:

0.408

AC:

6612

AN:

16192

Ashkenazi Jewish (ASJ)

AF:

0.350

AC:

3881

AN:

11102

East Asian (EAS)

AF:

0.370

AC:

9728

AN:

26264

South Asian (SAS)

AF:

0.297

AC:

10175

AN:

34234

European-Finnish (FIN)

AF:

0.357

AC:

8611

AN:

24142

Middle Eastern (MID)

AF:

0.334

AC:

673

AN:

2012

European-Non Finnish (NFE)

AF:

0.357

AC:

89976

AN:

252056

Other (OTH)

AF:

0.363

AC:

7807

AN:

21522

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.428

Heterozygous variant carriers

4588

9176

13763

18351

22939

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1350

2700

4050

5400

6750

<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:

0.744

AC:

100265

AN:

134726

Hom.:

37276

Cov.:

AF XY:

0.742

AC XY:

47675

AN XY:

64216

show subpopulations

African (AFR)

AF:

0.777

AC:

28195

AN:

36274

American (AMR)

AF:

0.834

AC:

11221

AN:

13450

Ashkenazi Jewish (ASJ)

AF:

0.712

AC:

2359

AN:

3314

East Asian (EAS)

AF:

0.713

AC:

3318

AN:

4652

South Asian (SAS)

AF:

0.636

AC:

2549

AN:

4006

European-Finnish (FIN)

AF:

0.701

AC:

4623

AN:

6596

Middle Eastern (MID)

AF:

0.725

AC:

187

AN:

258

European-Non Finnish (NFE)

AF:

0.721

AC:

45763

AN:

63498

Other (OTH)

AF:

0.757

AC:

1368

AN:

1806

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

1125

2251

3376

4502

5627

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

734

1468

2202

2936

3670

<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:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.53

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