Variant 2-110144616-A-G 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 ENST00000445609.7(NPHP1):c.1353-47T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0182 in 1,111,680 control chromosomes in the GnomAD database, including 2,200 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.073 ( 1319 hom., cov: 32)

Exomes 𝑓: 0.0095 ( 881 hom. )

Consequence

NPHP1
ENST00000445609.7 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.414

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=-0.92).

BP6

Variant 2-110144616-A-G is Benign according to our data. Variant chr2-110144616-A-G is described in ClinVar as [Benign]. Clinvar id is 255707.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.245 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.1353-47T>C		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.1353-47T>C		intron_variant		1	NM_001128178.3	ENSP00000389879	P2	O15259-2

Frequencies

GnomAD3 genomes

AF:

0.0729

AC:

11087

AN:

152134

Hom.:

1317

Cov.:

show subpopulations

Gnomad AFR

AF:

0.249

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0304

Gnomad ASJ

AF:

0.0176

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.000566

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00143

Gnomad OTH

AF:

0.0637

GnomAD3 exomes

AF:

0.0200

AC:

4896

AN:

245254

Hom.:

527

AF XY:

0.0150

AC XY:

1996

AN XY:

132778

show subpopulations

Gnomad AFR exome

AF:

0.257

Gnomad AMR exome

AF:

0.0142

Gnomad ASJ exome

AF:

0.0166

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000632

Gnomad FIN exome

AF:

0.000421

Gnomad NFE exome

AF:

0.00164

Gnomad OTH exome

AF:

0.0105

GnomAD4 exome

AF:

0.00954

AC:

9150

AN:

959428

Hom.:

881

Cov.:

AF XY:

0.00802

AC XY:

4008

AN XY:

499640

show subpopulations

Gnomad4 AFR exome

AF:

0.261

Gnomad4 AMR exome

AF:

0.0152

Gnomad4 ASJ exome

AF:

0.0158

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000670

Gnomad4 FIN exome

AF:

0.000586

Gnomad4 NFE exome

AF:

0.00106

Gnomad4 OTH exome

AF:

0.0211

GnomAD4 genome

AF:

0.0730

AC:

11109

AN:

152252

Hom.:

1319

Cov.:

AF XY:

0.0707

AC XY:

5264

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.249

Gnomad4 AMR

AF:

0.0304

Gnomad4 ASJ

AF:

0.0176

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.000566

Gnomad4 NFE

AF:

0.00141

Gnomad4 OTH

AF:

0.0630

Alfa

AF:

0.0355

Hom.:

163

Bravo

AF:

0.0822

Asia WGS

AF:

0.0160

AC:

AN:

3476

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 15, 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

-0.92

CADD

Benign

0.19

DANN

Benign

0.42

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