1-179551119-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014625.4(NPHS2):c.*54G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.619 in 1,607,334 control chromosomes in the GnomAD database, including 309,162 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.61 ( 28879 hom., cov: 31)

Exomes 𝑓: 0.62 ( 280283 hom. )

Consequence

NPHS2
NM_014625.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.952

Publications

11 publications found

Variant links:

Genes affected

NPHS2 (HGNC:13394): (NPHS2 stomatin family member, podocin) This gene encodes a protein that plays a role in the regulation of glomerular permeability. Mutations in this gene cause steroid-resistant nephrotic syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

NPHS2 links:

AXDND1 (HGNC:26564): (axonemal dynein light chain domain containing 1)

AXDND1 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=-0.9).

BP6

Variant 1-179551119-C-G is Benign according to our data. Variant chr1-179551119-C-G is described in ClinVar as [Benign]. Clinvar id is 293845.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPHS2	NM_014625.4 link	c.*54G>C		3_prime_UTR_variant	Exon 8 of 8	ENST00000367615.9	NP_055440.1	Q9NP85-1
AXDND1	NM_144696.6 link	c.3032-3393C>G		intron_variant	Intron 25 of 25	ENST00000367618.8	NP_653297.3	Q5T1B0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPHS2	ENST00000367615.9 link	c.*54G>C		3_prime_UTR_variant	Exon 8 of 8	1	NM_014625.4	ENSP00000356587.4		Q9NP85-1
AXDND1	ENST00000367618.8 link	c.3032-3393C>G		intron_variant	Intron 25 of 25	1	NM_144696.6	ENSP00000356590.3		Q5T1B0-1

Frequencies

GnomAD3 genomes

AF:

0.615

AC:

93387

AN:

151920

Hom.:

28851

Cov.:

show subpopulations

Gnomad AFR

AF:

0.604

Gnomad AMI

AF:

0.647

Gnomad AMR

AF:

0.638

Gnomad ASJ

AF:

0.640

Gnomad EAS

AF:

0.468

Gnomad SAS

AF:

0.591

Gnomad FIN

AF:

0.620

Gnomad MID

AF:

0.604

Gnomad NFE

AF:

0.626

Gnomad OTH

AF:

0.608

GnomAD4 exome

AF:

0.620

AC:

901687

AN:

1455296

Hom.:

280283

Cov.:

AF XY:

0.620

AC XY:

448858

AN XY:

724316

show subpopulations

African (AFR)

AF:

0.601

AC:

20049

AN:

33370

American (AMR)

AF:

0.664

AC:

29640

AN:

44646

Ashkenazi Jewish (ASJ)

AF:

0.659

AC:

17193

AN:

26094

East Asian (EAS)

AF:

0.507

AC:

20098

AN:

39648

South Asian (SAS)

AF:

0.602

AC:

51736

AN:

85910

European-Finnish (FIN)

AF:

0.624

AC:

32612

AN:

52254

Middle Eastern (MID)

AF:

0.654

AC:

3754

AN:

5740

European-Non Finnish (NFE)

AF:

0.622

AC:

689339

AN:

1107446

Other (OTH)

AF:

0.619

AC:

37266

AN:

60188

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

19194

38389

57583

76778

95972

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.615

AC:

93471

AN:

152038

Hom.:

28879

Cov.:

AF XY:

0.613

AC XY:

45580

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.604

AC:

25028

AN:

41452

American (AMR)

AF:

0.639

AC:

9763

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.640

AC:

2221

AN:

3470

East Asian (EAS)

AF:

0.468

AC:

2418

AN:

5162

South Asian (SAS)

AF:

0.591

AC:

2846

AN:

4814

European-Finnish (FIN)

AF:

0.620

AC:

6560

AN:

10574

Middle Eastern (MID)

AF:

0.609

AC:

179

AN:

294

European-Non Finnish (NFE)

AF:

0.626

AC:

42582

AN:

67970

Other (OTH)

AF:

0.609

AC:

1284

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1838

3676

5515

7353

9191

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.509

Hom.:

1425

Bravo

AF:

0.617

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Nephrotic syndrome, type 2

Benign:2

Jul 08, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:2

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 81% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 75. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

4.2

(source)

DANN

Benign

0.44

PhyloP100

0.95

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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1-179551119-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over