Genetic Variant ENST00000394282.8:c.132+10A>G (chr16-58487860-A-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2

The ENST00000394282.8(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
ENST00000394282.8 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0200

Publications

1 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 -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 VariationId is 1316367.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000394282.8. 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.132+10A>G	intron	N/A	NP_001365261.1
NDRG4	NM_001378333.1	c.132+10A>G	intron	N/A	NP_001365262.1
NDRG4	NM_001378334.1	c.132+10A>G	intron	N/A	NP_001365263.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NDRG4	ENST00000394282.8	TSL:1	c.132+10A>G	intron	N/A	ENSP00000377823.4	Q9ULP0-6
NDRG4	ENST00000258187.9	TSL:1	c.72+10A>G	intron	N/A	ENSP00000258187.5	Q9ULP0-3
NDRG4	ENST00000394279.6	TSL:5	c.72+10A>G	intron	N/A	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

GnomAD2 exomes

AF:

0.00773

AC:

1048

AN:

135616

AF XY:

0.00814

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 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

African (AFR)

AF:

0.00146

AC:

AN:

30798

American (AMR)

AF:

0.00326

AC:

111

AN:

34028

Ashkenazi Jewish (ASJ)

AF:

0.00936

AC:

231

AN:

24672

East Asian (EAS)

AF:

0.0000860

AC:

AN:

34872

South Asian (SAS)

AF:

0.00739

AC:

570

AN:

77092

European-Finnish (FIN)

AF:

0.00960

AC:

460

AN:

47902

Middle Eastern (MID)

AF:

0.00192

AC:

AN:

4170

European-Non Finnish (NFE)

AF:

0.0126

AC:

13474

AN:

1065860

Other (OTH)

AF:

0.0104

AC:

593

AN:

56836

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

733

1466

2200

2933

3666

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

514

1028

1542

2056

2570

<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:

0.00748

AC:

1139

AN:

152244

Hom.:

Cov.:

AF XY:

0.00717

AC XY:

534

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.00224

AC:

AN:

41548

American (AMR)

AF:

0.00425

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00922

AC:

AN:

3472

East Asian (EAS)

AF:

0.000969

AC:

AN:

5158

South Asian (SAS)

AF:

0.00498

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00800

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0120

AC:

814

AN:

68006

Other (OTH)

AF:

0.00805

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

107

161

214

268

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0106

Hom.:

Bravo

AF:

0.00693

Asia WGS

AF:

0.00635

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely 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

-0.44

CADD

Benign

9.5

(source)

DANN

Benign

0.79

PhyloP100

0.020

Mutation Taster

=100/0

polymorphism

(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