Variant rs201335783 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The ENST00000378156.9(NPHP4):c.3559-19del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00393 in 1,489,700 control chromosomes in the GnomAD database, including 17 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0029 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0040 ( 17 hom. )

Consequence

NPHP4
ENST00000378156.9 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.0860

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 -16 ACMG points.

BP6

Variant 1-5866476-AG-A is Benign according to our data. Variant chr1-5866476-AG-A is described in ClinVar as [Likely_benign]. Clinvar id is 260558.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-5866476-AG-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00287 (438/152354) while in subpopulation AMR AF= 0.00562 (86/15310). AF 95% confidence interval is 0.00466. There are 0 homozygotes in gnomad4. There are 226 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPHP4	NM_015102.5 linkuse as main transcript	c.3559-19del		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.3559-19del		intron_variant		1	NM_015102.5	ENSP00000367398	P2	O75161-1

Frequencies

GnomAD3 genomes

AF:

0.00288

AC:

439

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000796

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.00562

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00431

Gnomad OTH

AF:

0.00716

GnomAD3 exomes

AF:

0.00252

AC:

508

AN:

201376

Hom.:

AF XY:

0.00266

AC XY:

289

AN XY:

108722

show subpopulations

Gnomad AFR exome

AF:

0.000708

Gnomad AMR exome

AF:

0.00276

Gnomad ASJ exome

AF:

0.000762

Gnomad EAS exome

AF:

0.0000691

Gnomad SAS exome

AF:

0.000156

Gnomad FIN exome

AF:

0.000481

Gnomad NFE exome

AF:

0.00441

Gnomad OTH exome

AF:

0.00251

GnomAD4 exome

AF:

0.00405

AC:

5410

AN:

1337346

Hom.:

Cov.:

AF XY:

0.00392

AC XY:

2620

AN XY:

668128

show subpopulations

Gnomad4 AFR exome

AF:

0.000701

Gnomad4 AMR exome

AF:

0.00280

Gnomad4 ASJ exome

AF:

0.000560

Gnomad4 EAS exome

AF:

0.0000265

Gnomad4 SAS exome

AF:

0.000275

Gnomad4 FIN exome

AF:

0.000292

Gnomad4 NFE exome

AF:

0.00501

Gnomad4 OTH exome

AF:

0.00281

GnomAD4 genome

AF:

0.00287

AC:

438

AN:

152354

Hom.:

Cov.:

AF XY:

0.00303

AC XY:

226

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.000794

Gnomad4 AMR

AF:

0.00562

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00429

Gnomad4 OTH

AF:

0.00709

Alfa

AF:

0.00171

Hom.:

Bravo

AF:

0.00341

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Nephronophthisis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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