Variant 1-5866447-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_015102.5(NPHP4):c.3570A>G(p.Glu1190=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 1,588,154 control chromosomes in the GnomAD database, including 131,883 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 10239 hom., cov: 32)

Exomes 𝑓: 0.41 ( 121644 hom. )

Consequence

NPHP4
NM_015102.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.305

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 1-5866447-T-C is Benign according to our data. Variant chr1-5866447-T-C is described in ClinVar as [Benign]. Clinvar id is 95683.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-5866447-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.305 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPHP4	NM_015102.5 linkuse as main transcript	c.3570A>G	p.Glu1190=	synonymous_variant	26/30	ENST00000378156.9	NP_055917.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPHP4	ENST00000378156.9 linkuse as main transcript	c.3570A>G	p.Glu1190=	synonymous_variant	26/30	1	NM_015102.5	ENSP00000367398	P2	O75161-1

Frequencies

GnomAD3 genomes

AF:

0.354

AC:

53741

AN:

151904

Hom.:

10237

Cov.:

show subpopulations

Gnomad AFR

AF:

0.208

Gnomad AMI

AF:

0.549

Gnomad AMR

AF:

0.369

Gnomad ASJ

AF:

0.461

Gnomad EAS

AF:

0.271

Gnomad SAS

AF:

0.430

Gnomad FIN

AF:

0.428

Gnomad MID

AF:

0.392

Gnomad NFE

AF:

0.420

Gnomad OTH

AF:

0.362

GnomAD3 exomes

AF:

0.393

AC:

87822

AN:

223688

Hom.:

17546

AF XY:

0.398

AC XY:

48147

AN XY:

121048

show subpopulations

Gnomad AFR exome

AF:

0.200

Gnomad AMR exome

AF:

0.371

Gnomad ASJ exome

AF:

0.470

Gnomad EAS exome

AF:

0.256

Gnomad SAS exome

AF:

0.430

Gnomad FIN exome

AF:

0.426

Gnomad NFE exome

AF:

0.422

Gnomad OTH exome

AF:

0.407

GnomAD4 exome

AF:

0.408

AC:

585860

AN:

1436130

Hom.:

121644

Cov.:

AF XY:

0.409

AC XY:

291912

AN XY:

713438

show subpopulations

Gnomad4 AFR exome

AF:

0.199

Gnomad4 AMR exome

AF:

0.369

Gnomad4 ASJ exome

AF:

0.461

Gnomad4 EAS exome

AF:

0.266

Gnomad4 SAS exome

AF:

0.431

Gnomad4 FIN exome

AF:

0.426

Gnomad4 NFE exome

AF:

0.417

Gnomad4 OTH exome

AF:

0.402

GnomAD4 genome

AF:

0.354

AC:

53764

AN:

152024

Hom.:

10239

Cov.:

AF XY:

0.356

AC XY:

26423

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.209

Gnomad4 AMR

AF:

0.369

Gnomad4 ASJ

AF:

0.461

Gnomad4 EAS

AF:

0.271

Gnomad4 SAS

AF:

0.430

Gnomad4 FIN

AF:

0.428

Gnomad4 NFE

AF:

0.420

Gnomad4 OTH

AF:

0.358

Alfa

AF:

0.407

Hom.:

14630

Bravo

AF:

0.340

Asia WGS

AF:

0.377

AC:

1310

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

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Oct 01, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Nephronophthisis 4

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Senior-Loken syndrome 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Nephronophthisis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

1.2

DANN

Benign

0.45

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