rs3747992

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_015102.5(NPHP4):c.2802C>T(p.Arg934Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 1,575,438 control chromosomes in the GnomAD database, including 129,927 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 11523 hom., cov: 34)

Exomes 𝑓: 0.40 ( 118404 hom. )

Consequence

NPHP4
NM_015102.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -0.507

Publications

30 publications found

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 Gene-Disease associations (from GenCC):

nephronophthisis 4
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), G2P
Senior-Loken syndrome 4
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
nephronophthisis 1
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Senior-Loken syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

NPHP4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 1-5877108-G-A is Benign according to our data. Variant chr1-5877108-G-A is described in ClinVar as Benign. ClinVar VariationId is 95679.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.507 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPHP4	NM_015102.5 link	c.2802C>T	p.Arg934Arg	synonymous_variant	Exon 20 of 30	ENST00000378156.9	NP_055917.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NPHP4	ENST00000378156.9 link	c.2802C>T	p.Arg934Arg	synonymous_variant	Exon 20 of 30	1	NM_015102.5	ENSP00000367398.4	O75161-1
NPHP4	ENST00000378169.7 link	n.*1703C>T		non_coding_transcript_exon_variant	Exon 17 of 27	1		ENSP00000367411.3	D6RA06
NPHP4	ENST00000489180.6 link	n.*350C>T		non_coding_transcript_exon_variant	Exon 21 of 33	2		ENSP00000423747.1	O75161-2
NPHP4	ENST00000378169.7 link	n.*1703C>T		3_prime_UTR_variant	Exon 17 of 27	1		ENSP00000367411.3	D6RA06
NPHP4	ENST00000489180.6 link	n.*350C>T		3_prime_UTR_variant	Exon 21 of 33	2		ENSP00000423747.1	O75161-2

Frequencies

GnomAD3 genomes

AF:

0.378

AC:

57511

AN:

151998

Hom.:

11520

Cov.:

show subpopulations

Gnomad AFR

AF:

0.285

Gnomad AMI

AF:

0.317

Gnomad AMR

AF:

0.438

Gnomad ASJ

AF:

0.369

Gnomad EAS

AF:

0.743

Gnomad SAS

AF:

0.425

Gnomad FIN

AF:

0.391

Gnomad MID

AF:

0.323

Gnomad NFE

AF:

0.390

Gnomad OTH

AF:

0.380

GnomAD2 exomes

AF:

0.431

AC:

100525

AN:

233474

AF XY:

0.428

show subpopulations

Gnomad AFR exome

AF:

0.287

Gnomad AMR exome

AF:

0.514

Gnomad ASJ exome

AF:

0.372

Gnomad EAS exome

AF:

0.760

Gnomad FIN exome

AF:

0.394

Gnomad NFE exome

AF:

0.387

Gnomad OTH exome

AF:

0.402

GnomAD4 exome

AF:

0.402

AC:

572042

AN:

1423322

Hom.:

118404

Cov.:

AF XY:

0.402

AC XY:

282278

AN XY:

701630

show subpopulations

African (AFR)

AF:

0.273

AC:

8972

AN:

32874

American (AMR)

AF:

0.506

AC:

21865

AN:

43188

Ashkenazi Jewish (ASJ)

AF:

0.374

AC:

9435

AN:

25210

East Asian (EAS)

AF:

0.747

AC:

28809

AN:

38548

South Asian (SAS)

AF:

0.415

AC:

34443

AN:

82968

European-Finnish (FIN)

AF:

0.390

AC:

20407

AN:

52310

Middle Eastern (MID)

AF:

0.345

AC:

1829

AN:

5300

European-Non Finnish (NFE)

AF:

0.390

AC:

422691

AN:

1084378

Other (OTH)

AF:

0.403

AC:

23591

AN:

58546

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

15546

31093

46639

62186

77732

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13670

27340

41010

54680

68350

<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:

0.378

AC:

57535

AN:

152116

Hom.:

11523

Cov.:

AF XY:

0.382

AC XY:

28381

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.285

AC:

11813

AN:

41512

American (AMR)

AF:

0.438

AC:

6698

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.369

AC:

1280

AN:

3468

East Asian (EAS)

AF:

0.744

AC:

3838

AN:

5160

South Asian (SAS)

AF:

0.425

AC:

2051

AN:

4826

European-Finnish (FIN)

AF:

0.391

AC:

4133

AN:

10564

Middle Eastern (MID)

AF:

0.323

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.390

AC:

26537

AN:

67980

Other (OTH)

AF:

0.379

AC:

801

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1800

3600

5400

7200

9000

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

558

1116

1674

2232

2790

<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:

0.383

Hom.:

17245

Bravo

AF:

0.380

Asia WGS

AF:

0.501

AC:

1742

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jan 27, 2016

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 04, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Mar 24, 2020

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

-0.80

CADD

Benign

3.1

(source)

DANN

Benign

0.52

PhyloP100

-0.51

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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