chr1-179551287-T-C

Position:

chr1-179551287-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_014625.4(NPHS2):c.1038A>G(p.Leu346=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0845 in 1,613,852 control chromosomes in the GnomAD database, including 6,329 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.084 ( 610 hom., cov: 32)

Exomes 𝑓: 0.085 ( 5719 hom. )

Consequence

NPHS2
NM_014625.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.0750

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 made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 1-179551287-T-C is Benign according to our data. Variant chr1-179551287-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 260425.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-179551287-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.075 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0867 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.1038A>G	p.Leu346=	synonymous_variant	8/8	ENST00000367615.9	NP_055440.1
AXDND1	NM_144696.6 linkuse as main transcript	c.3032-3225T>C		intron_variant		ENST00000367618.8	NP_653297.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPHS2	ENST00000367615.9 linkuse as main transcript	c.1038A>G	p.Leu346=	synonymous_variant	8/8	1	NM_014625.4	ENSP00000356587	P1	Q9NP85-1
AXDND1	ENST00000367618.8 linkuse as main transcript	c.3032-3225T>C		intron_variant		1	NM_144696.6	ENSP00000356590	P2	Q5T1B0-1

Frequencies

GnomAD3 genomes

AF:

0.0845

AC:

12833

AN:

151884

Hom.:

610

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0892

Gnomad AMI

AF:

0.112

Gnomad AMR

AF:

0.0594

Gnomad ASJ

AF:

0.0746

Gnomad EAS

AF:

0.0888

Gnomad SAS

AF:

0.0141

Gnomad FIN

AF:

0.130

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0854

Gnomad OTH

AF:

0.0796

GnomAD3 exomes

AF:

0.0735

AC:

18453

AN:

251196

Hom.:

907

AF XY:

0.0706

AC XY:

9590

AN XY:

135742

show subpopulations

Gnomad AFR exome

AF:

0.0904

Gnomad AMR exome

AF:

0.0355

Gnomad ASJ exome

AF:

0.0633

Gnomad EAS exome

AF:

0.0938

Gnomad SAS exome

AF:

0.0144

Gnomad FIN exome

AF:

0.131

Gnomad NFE exome

AF:

0.0851

Gnomad OTH exome

AF:

0.0767

GnomAD4 exome

AF:

0.0845

AC:

123590

AN:

1461850

Hom.:

5719

Cov.:

AF XY:

0.0818

AC XY:

59517

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.0860

Gnomad4 AMR exome

AF:

0.0376

Gnomad4 ASJ exome

AF:

0.0645

Gnomad4 EAS exome

AF:

0.0673

Gnomad4 SAS exome

AF:

0.0137

Gnomad4 FIN exome

AF:

0.131

Gnomad4 NFE exome

AF:

0.0912

Gnomad4 OTH exome

AF:

0.0831

GnomAD4 genome

AF:

0.0845

AC:

12841

AN:

152002

Hom.:

610

Cov.:

AF XY:

0.0837

AC XY:

6218

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.0891

Gnomad4 AMR

AF:

0.0593

Gnomad4 ASJ

AF:

0.0746

Gnomad4 EAS

AF:

0.0890

Gnomad4 SAS

AF:

0.0139

Gnomad4 FIN

AF:

0.130

Gnomad4 NFE

AF:

0.0854

Gnomad4 OTH

AF:

0.0792

Alfa

AF:

0.0806

Hom.:

727

Bravo

AF:

0.0800

Asia WGS

AF:

0.0390

AC:

136

AN:

3478

EpiCase

AF:

0.0768

EpiControl

AF:

0.0756

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Nephrotic syndrome, type 2

Benign:3

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 29, 2017	- -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Mar 06, 2018	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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -
Likely benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Apr 11, 2023	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 05, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Steroid-resistant nephrotic syndrome

Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Sep 16, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

5.0

DANN

Benign

0.55

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