Variant rs868163 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.3231+41T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.634 in 1,468,040 control chromosomes in the GnomAD database, including 299,087 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.64 ( 31664 hom., cov: 31)

Exomes 𝑓: 0.63 ( 267423 hom. )

Consequence

NPHP4
NM_015102.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.93

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=-0.92).

BP6

Variant 1-5874430-A-G is Benign according to our data. Variant chr1-5874430-A-G is described in ClinVar as [Benign]. Clinvar id is 260554.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPHP4	NM_015102.5 linkuse as main transcript	c.3231+41T>C		intron_variant		ENST00000378156.9

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
NPHP4	ENST00000378156.9 linkuse as main transcript	c.3231+41T>C	intron_variant	1	NM_015102.5	P2	O75161-1
NPHP4	ENST00000378169.7 linkuse as main transcript	c.*2132+41T>C	intron_variant, NMD_transcript_variant	1
NPHP4	ENST00000489180.6 linkuse as main transcript	c.*1042+41T>C	intron_variant, NMD_transcript_variant	2			O75161-2
NPHP4	ENST00000478423.6 linkuse as main transcript	n.2963+41T>C	intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.640

AC:

96960

AN:

151466

Hom.:

31634

Cov.:

show subpopulations

Gnomad AFR

AF:

0.706

Gnomad AMI

AF:

0.743

Gnomad AMR

AF:

0.562

Gnomad ASJ

AF:

0.642

Gnomad EAS

AF:

0.289

Gnomad SAS

AF:

0.614

Gnomad FIN

AF:

0.644

Gnomad MID

AF:

0.669

Gnomad NFE

AF:

0.645

Gnomad OTH

AF:

0.623

GnomAD3 exomes

AF:

0.588

AC:

61027

AN:

103766

Hom.:

18769

AF XY:

0.587

AC XY:

31497

AN XY:

53644

show subpopulations

Gnomad AFR exome

AF:

0.713

Gnomad AMR exome

AF:

0.499

Gnomad ASJ exome

AF:

0.648

Gnomad EAS exome

AF:

0.269

Gnomad SAS exome

AF:

0.615

Gnomad FIN exome

AF:

0.638

Gnomad NFE exome

AF:

0.644

Gnomad OTH exome

AF:

0.610

GnomAD4 exome

AF:

0.634

AC:

834220

AN:

1316454

Hom.:

267423

Cov.:

AF XY:

0.633

AC XY:

405729

AN XY:

641076

show subpopulations

Gnomad4 AFR exome

AF:

0.717

Gnomad4 AMR exome

AF:

0.507

Gnomad4 ASJ exome

AF:

0.646

Gnomad4 EAS exome

AF:

0.290

Gnomad4 SAS exome

AF:

0.624

Gnomad4 FIN exome

AF:

0.645

Gnomad4 NFE exome

AF:

0.647

Gnomad4 OTH exome

AF:

0.622

GnomAD4 genome

AF:

0.640

AC:

97041

AN:

151586

Hom.:

31664

Cov.:

AF XY:

0.636

AC XY:

47073

AN XY:

74050

show subpopulations

Gnomad4 AFR

AF:

0.706

Gnomad4 AMR

AF:

0.562

Gnomad4 ASJ

AF:

0.642

Gnomad4 EAS

AF:

0.288

Gnomad4 SAS

AF:

0.613

Gnomad4 FIN

AF:

0.644

Gnomad4 NFE

AF:

0.645

Gnomad4 OTH

AF:

0.624

Alfa

AF:

0.638

Hom.:

34807

Bravo

AF:

0.634

Asia WGS

AF:

0.514

AC:

1788

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 13, 2021

- -

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

-0.92

CADD

Benign

0.042

DANN

Benign

0.22

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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