rs7520105

Variant names:

Variant summary

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

The NM_015102.5(NPHP4):c.1441+13A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 1,595,044 control chromosomes in the GnomAD database, including 21,666 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2301 hom., cov: 32)

Exomes 𝑓: 0.16 ( 19365 hom. )

Consequence

NPHP4
NM_015102.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.540

Variant links:

Genes affected

NPHP4 (HGNC:19104): (nephrocystin 4) This gene encodes a protein involved in renal tubular development and function. This protein interacts with nephrocystin, and belongs to a multifunctional complex that is localized to actin- and microtubule-based structures. Mutations in this gene are associated with nephronophthisis type 4, a renal disease, and with Senior-Loken syndrome type 4, a combination of nephronophthisis and retinitis pigmentosa. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2014]

NPHP4 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=-0.83).

BP6

Variant 1-5927636-T-C is Benign according to our data. Variant chr1-5927636-T-C is described in ClinVar as [Benign]. Clinvar id is 95671.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-5927636-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPHP4	NM_015102.5 link	c.1441+13A>G		intron_variant	Intron 11 of 29	ENST00000378156.9	NP_055917.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
NPHP4	ENST00000378156.9 link	c.1441+13A>G	intron_variant	Intron 11 of 29	1	NM_015102.5	ENSP00000367398.4	O75161-1
NPHP4	ENST00000378169.7 link	n.*515+13A>G	intron_variant	Intron 10 of 26	1		ENSP00000367411.3	D6RA06
NPHP4	ENST00000489180.6 link	n.1441+13A>G	intron_variant	Intron 11 of 32	2		ENSP00000423747.1	O75161-2

Frequencies

GnomAD3 genomes

AF:

0.171

AC:

25985

AN:

152042

Hom.:

2301

Cov.:

show subpopulations

Gnomad AFR

AF:

0.215

Gnomad AMI

AF:

0.160

Gnomad AMR

AF:

0.134

Gnomad ASJ

AF:

0.224

Gnomad EAS

AF:

0.0751

Gnomad SAS

AF:

0.122

Gnomad FIN

AF:

0.130

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.167

Gnomad OTH

AF:

0.184

GnomAD3 exomes

AF:

0.145

AC:

35805

AN:

246092

Hom.:

2852

AF XY:

0.146

AC XY:

19475

AN XY:

133538

show subpopulations

Gnomad AFR exome

AF:

0.210

Gnomad AMR exome

AF:

0.0875

Gnomad ASJ exome

AF:

0.221

Gnomad EAS exome

AF:

0.0770

Gnomad SAS exome

AF:

0.115

Gnomad FIN exome

AF:

0.137

Gnomad NFE exome

AF:

0.168

Gnomad OTH exome

AF:

0.155

GnomAD4 exome

AF:

0.161

AC:

232402

AN:

1442884

Hom.:

19365

Cov.:

AF XY:

0.160

AC XY:

114058

AN XY:

714284

show subpopulations

Gnomad4 AFR exome

AF:

0.215

Gnomad4 AMR exome

AF:

0.0938

Gnomad4 ASJ exome

AF:

0.218

Gnomad4 EAS exome

AF:

0.0765

Gnomad4 SAS exome

AF:

0.117

Gnomad4 FIN exome

AF:

0.141

Gnomad4 NFE exome

AF:

0.168

Gnomad4 OTH exome

AF:

0.166

GnomAD4 genome

AF:

0.171

AC:

26000

AN:

152160

Hom.:

2301

Cov.:

AF XY:

0.169

AC XY:

12547

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.214

Gnomad4 AMR

AF:

0.134

Gnomad4 ASJ

AF:

0.224

Gnomad4 EAS

AF:

0.0749

Gnomad4 SAS

AF:

0.122

Gnomad4 FIN

AF:

0.130

Gnomad4 NFE

AF:

0.167

Gnomad4 OTH

AF:

0.182

Alfa

AF:

0.177

Hom.:

474

Bravo

AF:

0.174

Asia WGS

AF:

0.109

AC:

378

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 01, 2013

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

May 13, 2021

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

- -

Nephronophthisis 4

Benign:2

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. -

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Senior-Loken syndrome 4

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Nephronophthisis

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

5.7

DANN

Benign

0.58

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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