Variant rs41280814 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_015102.5(NPHP4):c.2485+38C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 1,572,348 control chromosomes in the GnomAD database, including 19,477 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1362 hom., cov: 33)

Exomes 𝑓: 0.16 ( 18115 hom. )

Consequence

NPHP4
NM_015102.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.10

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=-0.85).

BP6

Variant 1-5887248-G-A is Benign according to our data. Variant chr1-5887248-G-A is described in ClinVar as [Benign]. Clinvar id is 260546.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.163 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.2485+38C>T		intron_variant		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.2485+38C>T		intron_variant		1	NM_015102.5	ENSP00000367398	P2	O75161-1

Frequencies

GnomAD3 genomes

AF:

0.118

AC:

17988

AN:

152154

Hom.:

1363

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0333

Gnomad AMI

AF:

0.161

Gnomad AMR

AF:

0.113

Gnomad ASJ

AF:

0.232

Gnomad EAS

AF:

0.0756

Gnomad SAS

AF:

0.120

Gnomad FIN

AF:

0.131

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.165

Gnomad OTH

AF:

0.136

GnomAD3 exomes

AF:

0.134

AC:

26627

AN:

198424

Hom.:

1991

AF XY:

0.138

AC XY:

14828

AN XY:

107794

show subpopulations

Gnomad AFR exome

AF:

0.0275

Gnomad AMR exome

AF:

0.0789

Gnomad ASJ exome

AF:

0.230

Gnomad EAS exome

AF:

0.0795

Gnomad SAS exome

AF:

0.116

Gnomad FIN exome

AF:

0.140

Gnomad NFE exome

AF:

0.172

Gnomad OTH exome

AF:

0.151

GnomAD4 exome

AF:

0.156

AC:

221859

AN:

1420076

Hom.:

18115

Cov.:

AF XY:

0.156

AC XY:

109355

AN XY:

702458

show subpopulations

Gnomad4 AFR exome

AF:

0.0269

Gnomad4 AMR exome

AF:

0.0833

Gnomad4 ASJ exome

AF:

0.223

Gnomad4 EAS exome

AF:

0.0788

Gnomad4 SAS exome

AF:

0.117

Gnomad4 FIN exome

AF:

0.143

Gnomad4 NFE exome

AF:

0.168

Gnomad4 OTH exome

AF:

0.155

GnomAD4 genome

AF:

0.118

AC:

17983

AN:

152272

Hom.:

1362

Cov.:

AF XY:

0.117

AC XY:

8728

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0333

Gnomad4 AMR

AF:

0.113

Gnomad4 ASJ

AF:

0.232

Gnomad4 EAS

AF:

0.0754

Gnomad4 SAS

AF:

0.120

Gnomad4 FIN

AF:

0.131

Gnomad4 NFE

AF:

0.165

Gnomad4 OTH

AF:

0.135

Alfa

AF:

0.152

Hom.:

389

Bravo

AF:

0.113

Asia WGS

AF:

0.102

AC:

353

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	clinical testing	GeneDx	May 13, 2021	- -
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

- -

Nephronophthisis 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.036

DANN

Benign

0.64

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