rs146343637

Positions:

chr2-110163152-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001128178.3(NPHP1):c.772-17G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00858 in 1,558,244 control chromosomes in the GnomAD database, including 145 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0084 ( 15 hom., cov: 32)

Exomes 𝑓: 0.0086 ( 130 hom. )

Consequence

NPHP1
NM_001128178.3 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.851

Variant links:

Genes affected

NPHP1 (HGNC:7905): (nephrocystin 1) This gene encodes a protein with src homology domain 3 (SH3) patterns. This protein interacts with Crk-associated substrate, and it appears to function in the control of cell division, as well as in cell-cell and cell-matrix adhesion signaling, likely as part of a multifunctional complex localized in actin- and microtubule-based structures. Mutations in this gene cause familial juvenile nephronophthisis type 1, a kidney disorder involving both tubules and glomeruli. Defects in this gene are also associated with Senior-Loken syndrome type 1, also referred to as juvenile nephronophthisis with Leber amaurosis, which is characterized by kidney and eye disease, and with Joubert syndrome type 4, which is characterized by cerebellar ataxia, oculomotor apraxia, psychomotor delay and neonatal breathing abnormalities, sometimes including retinal dystrophy and renal disease. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

NPHP1 links:

NPHP1 (HGNC:):

NPHP1 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=-0.86).

BP6

Variant 2-110163152-C-T is Benign according to our data. Variant chr2-110163152-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 199003.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-110163152-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00835 (1272/152250) while in subpopulation NFE AF= 0.00878 (597/68008). AF 95% confidence interval is 0.0082. There are 15 homozygotes in gnomad4. There are 674 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPHP1	NM_001128178.3 linkuse as main transcript	c.772-17G>A		intron_variant		ENST00000445609.7	NP_001121650.1	O15259-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPHP1	ENST00000445609.7 linkuse as main transcript	c.772-17G>A		intron_variant		1	NM_001128178.3	ENSP00000389879.3		O15259-2

Frequencies

GnomAD3 genomes

AF:

0.00836

AC:

1272

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000941

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00386

Gnomad ASJ

AF:

0.0297

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.00498

Gnomad FIN

AF:

0.0400

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00878

Gnomad OTH

AF:

0.00957

GnomAD3 exomes

AF:

0.0102

AC:

2567

AN:

250642

Hom.:

AF XY:

0.0105

AC XY:

1418

AN XY:

135380

show subpopulations

Gnomad AFR exome

AF:

0.000987

Gnomad AMR exome

AF:

0.00429

Gnomad ASJ exome

AF:

0.0287

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00479

Gnomad FIN exome

AF:

0.0444

Gnomad NFE exome

AF:

0.00830

Gnomad OTH exome

AF:

0.0111

GnomAD4 exome

AF:

0.00861

AC:

12105

AN:

1405994

Hom.:

130

Cov.:

AF XY:

0.00869

AC XY:

6108

AN XY:

702942

show subpopulations

Gnomad4 AFR exome

AF:

0.000862

Gnomad4 AMR exome

AF:

0.00414

Gnomad4 ASJ exome

AF:

0.0300

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00551

Gnomad4 FIN exome

AF:

0.0435

Gnomad4 NFE exome

AF:

0.00726

Gnomad4 OTH exome

AF:

0.00927

GnomAD4 genome

AF:

0.00835

AC:

1272

AN:

152250

Hom.:

Cov.:

AF XY:

0.00905

AC XY:

674

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.000938

Gnomad4 AMR

AF:

0.00386

Gnomad4 ASJ

AF:

0.0297

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.00498

Gnomad4 FIN

AF:

0.0400

Gnomad4 NFE

AF:

0.00878

Gnomad4 OTH

AF:

0.00947

Alfa

AF:

0.0127

Hom.:

Bravo

AF:

0.00504

Asia WGS

AF:

0.00231

AC:

AN:

3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Sep 18, 2014	- -

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 16, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2024	NPHP1: BS2 -

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

-0.86

CADD

Benign

DANN

Benign

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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