Variant rs12401708 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014625.4(NPHS2):c.452-21C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 1,505,300 control chromosomes in the GnomAD database, including 50,838 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3797 hom., cov: 32)

Exomes 𝑓: 0.26 ( 47041 hom. )

Consequence

NPHS2
NM_014625.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.0840

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 1-179559782-G-A is Benign according to our data. Variant chr1-179559782-G-A is described in ClinVar as [Benign]. Clinvar id is 1180466.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPHS2	NM_014625.4 linkuse as main transcript	c.452-21C>T		intron_variant		ENST00000367615.9	NP_055440.1	Q9NP85-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPHS2	ENST00000367615.9 linkuse as main transcript	c.452-21C>T		intron_variant		1	NM_014625.4	ENSP00000356587.4		Q9NP85-1
NPHS2	ENST00000367616.4 linkuse as main transcript	c.452-21C>T		intron_variant		1		ENSP00000356588.4		Q9NP85-2

Frequencies

GnomAD3 genomes

AF:

0.202

AC:

30745

AN:

151988

Hom.:

3794

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0696

Gnomad AMI

AF:

0.202

Gnomad AMR

AF:

0.203

Gnomad ASJ

AF:

0.342

Gnomad EAS

AF:

0.0484

Gnomad SAS

AF:

0.193

Gnomad FIN

AF:

0.307

Gnomad MID

AF:

0.225

Gnomad NFE

AF:

0.272

Gnomad OTH

AF:

0.205

GnomAD3 exomes

AF:

0.238

AC:

41420

AN:

174312

Hom.:

5553

AF XY:

0.241

AC XY:

22167

AN XY:

92160

show subpopulations

Gnomad AFR exome

AF:

0.0633

Gnomad AMR exome

AF:

0.241

Gnomad ASJ exome

AF:

0.362

Gnomad EAS exome

AF:

0.0432

Gnomad SAS exome

AF:

0.202

Gnomad FIN exome

AF:

0.309

Gnomad NFE exome

AF:

0.275

Gnomad OTH exome

AF:

0.256

GnomAD4 exome

AF:

0.258

AC:

349490

AN:

1353192

Hom.:

47041

Cov.:

AF XY:

0.258

AC XY:

173169

AN XY:

671596

show subpopulations

Gnomad4 AFR exome

AF:

0.0600

Gnomad4 AMR exome

AF:

0.234

Gnomad4 ASJ exome

AF:

0.350

Gnomad4 EAS exome

AF:

0.0719

Gnomad4 SAS exome

AF:

0.208

Gnomad4 FIN exome

AF:

0.308

Gnomad4 NFE exome

AF:

0.272

Gnomad4 OTH exome

AF:

0.241

GnomAD4 genome

AF:

0.202

AC:

30761

AN:

152108

Hom.:

3797

Cov.:

AF XY:

0.203

AC XY:

15110

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.0694

Gnomad4 AMR

AF:

0.203

Gnomad4 ASJ

AF:

0.342

Gnomad4 EAS

AF:

0.0483

Gnomad4 SAS

AF:

0.194

Gnomad4 FIN

AF:

0.307

Gnomad4 NFE

AF:

0.272

Gnomad4 OTH

AF:

0.203

Alfa

AF:

0.260

Hom.:

1029

Bravo

AF:

0.188

Asia WGS

AF:

0.111

AC:

385

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Nephrotic syndrome, type 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 08, 2021

- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jul 15, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 41% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 38. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.7

DANN

Benign

0.53

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over