dbSNP rs114905610: NPHS2:c.*173G>A (chr1-179551000-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_014625.4(NPHS2):c.*173G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000881 in 746,556 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.0025 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00046 ( 2 hom. )

Consequence

NPHS2
NM_014625.4 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 1.16

Publications

1 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 -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BS2

High Homozygotes in GnomAdExome4 at 2 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014625.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NPHS2	NM_014625.4	MANE Select	c.*173G>A	3_prime_UTR	Exon 8 of 8	NP_055440.1	Q9NP85-1
AXDND1	NM_144696.6	MANE Select	c.3032-3512C>T	intron	N/A	NP_653297.3
NPHS2	NM_001297575.2		c.*173G>A	3_prime_UTR	Exon 7 of 7	NP_001284504.1	Q9NP85-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NPHS2	ENST00000367615.9	TSL:1 MANE Select	c.*173G>A	3_prime_UTR	Exon 8 of 8	ENSP00000356587.4	Q9NP85-1
NPHS2	ENST00000367616.4	TSL:1	c.*173G>A	3_prime_UTR	Exon 7 of 7	ENSP00000356588.4	Q9NP85-2
AXDND1	ENST00000367618.8	TSL:1 MANE Select	c.3032-3512C>T	intron	N/A	ENSP00000356590.3	Q5T1B0-1

Frequencies

GnomAD3 genomes

AF:

0.00252

AC:

384

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00818

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00239

GnomAD4 exome

AF:

0.000456

AC:

271

AN:

594230

Hom.:

Cov.:

AF XY:

0.000433

AC XY:

135

AN XY:

311972

show subpopulations

African (AFR)

AF:

0.0112

AC:

177

AN:

15854

American (AMR)

AF:

0.000783

AC:

AN:

28114

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16692

East Asian (EAS)

AF:

0.00

AC:

AN:

31882

South Asian (SAS)

AF:

0.0000186

AC:

AN:

53846

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32372

Middle Eastern (MID)

AF:

0.00333

AC:

AN:

2402

European-Non Finnish (NFE)

AF:

0.0000602

AC:

AN:

381912

Other (OTH)

AF:

0.00128

AC:

AN:

31156

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.00254

AC:

387

AN:

152326

Hom.:

Cov.:

AF XY:

0.00250

AC XY:

186

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.00823

AC:

342

AN:

41570

American (AMR)

AF:

0.00203

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000415

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68042

Other (OTH)

AF:

0.00237

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

108

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00129

Hom.:

Bravo

AF:

0.00295

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Nephrotic syndrome, type 2 (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.8

(source)

DANN

Benign

0.70

PhyloP100

1.2

Mutation Taster

=100/0

polymorphism

(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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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