Variant 2-110161744-C-T 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_001128178.3(NPHP1):c.860-47G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 1,368,978 control chromosomes in the GnomAD database, including 80,554 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 7601 hom., cov: 32)

Exomes 𝑓: 0.34 ( 72953 hom. )

Consequence

NPHP1
NM_001128178.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.185

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:

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=-0.8).

BP6

Variant 2-110161744-C-T is Benign according to our data. Variant chr2-110161744-C-T is described in ClinVar as [Benign]. Clinvar id is 255705.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPHP1	NM_001128178.3 linkuse as main transcript	c.860-47G>A		intron_variant		ENST00000445609.7	NP_001121650.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPHP1	ENST00000445609.7 linkuse as main transcript	c.860-47G>A		intron_variant		1	NM_001128178.3	ENSP00000389879	P2	O15259-2

Frequencies

GnomAD3 genomes

AF:

0.301

AC:

45716

AN:

151782

Hom.:

7583

Cov.:

show subpopulations

Gnomad AFR

AF:

0.203

Gnomad AMI

AF:

0.348

Gnomad AMR

AF:

0.371

Gnomad ASJ

AF:

0.314

Gnomad EAS

AF:

0.561

Gnomad SAS

AF:

0.492

Gnomad FIN

AF:

0.224

Gnomad MID

AF:

0.389

Gnomad NFE

AF:

0.322

Gnomad OTH

AF:

0.309

GnomAD3 exomes

AF:

0.354

AC:

77416

AN:

218922

Hom.:

14551

AF XY:

0.363

AC XY:

42990

AN XY:

118432

show subpopulations

Gnomad AFR exome

AF:

0.203

Gnomad AMR exome

AF:

0.349

Gnomad ASJ exome

AF:

0.313

Gnomad EAS exome

AF:

0.576

Gnomad SAS exome

AF:

0.496

Gnomad FIN exome

AF:

0.229

Gnomad NFE exome

AF:

0.329

Gnomad OTH exome

AF:

0.342

GnomAD4 exome

AF:

0.337

AC:

409664

AN:

1217078

Hom.:

72953

Cov.:

AF XY:

0.342

AC XY:

210951

AN XY:

616158

show subpopulations

Gnomad4 AFR exome

AF:

0.201

Gnomad4 AMR exome

AF:

0.349

Gnomad4 ASJ exome

AF:

0.314

Gnomad4 EAS exome

AF:

0.579

Gnomad4 SAS exome

AF:

0.490

Gnomad4 FIN exome

AF:

0.230

Gnomad4 NFE exome

AF:

0.323

Gnomad4 OTH exome

AF:

0.335

GnomAD4 genome

AF:

0.301

AC:

45783

AN:

151900

Hom.:

7601

Cov.:

AF XY:

0.306

AC XY:

22688

AN XY:

74250

show subpopulations

Gnomad4 AFR

AF:

0.203

Gnomad4 AMR

AF:

0.372

Gnomad4 ASJ

AF:

0.314

Gnomad4 EAS

AF:

0.561

Gnomad4 SAS

AF:

0.493

Gnomad4 FIN

AF:

0.224

Gnomad4 NFE

AF:

0.322

Gnomad4 OTH

AF:

0.309

Alfa

AF:

0.322

Hom.:

4561

Bravo

AF:

0.303

Asia WGS

AF:

0.479

AC:

1665

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 06, 2018	- -
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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

9.2

DANN

Benign

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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