Variant chr1-5874440-T-C 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+31A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 1,486,024 control chromosomes in the GnomAD database, including 47,350 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 3940 hom., cov: 32)

Exomes 𝑓: 0.25 ( 43410 hom. )

Consequence

NPHP4
NM_015102.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.08

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 1-5874440-T-C is Benign according to our data. Variant chr1-5874440-T-C is described in ClinVar as [Benign]. Clinvar id is 260553.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPHP4	NM_015102.5 linkuse as main transcript	c.3231+31A>G		intron_variant		ENST00000378156.9	NP_055917.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
NPHP4	ENST00000378156.9 linkuse as main transcript	c.3231+31A>G	intron_variant	1	NM_015102.5	ENSP00000367398	P2	O75161-1
NPHP4	ENST00000378169.7 linkuse as main transcript	c.*2132+31A>G	intron_variant, NMD_transcript_variant	1		ENSP00000367411
NPHP4	ENST00000489180.6 linkuse as main transcript	c.*1042+31A>G	intron_variant, NMD_transcript_variant	2		ENSP00000423747		O75161-2
NPHP4	ENST00000478423.6 linkuse as main transcript	n.2963+31A>G	intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.215

AC:

32693

AN:

151922

Hom.:

3941

Cov.:

show subpopulations

Gnomad AFR

AF:

0.102

Gnomad AMI

AF:

0.264

Gnomad AMR

AF:

0.273

Gnomad ASJ

AF:

0.224

Gnomad EAS

AF:

0.410

Gnomad SAS

AF:

0.430

Gnomad FIN

AF:

0.232

Gnomad MID

AF:

0.283

Gnomad NFE

AF:

0.237

Gnomad OTH

AF:

0.216

GnomAD3 exomes

AF:

0.272

AC:

30953

AN:

113764

Hom.:

4706

AF XY:

0.280

AC XY:

16699

AN XY:

59684

show subpopulations

Gnomad AFR exome

AF:

0.0996

Gnomad AMR exome

AF:

0.313

Gnomad ASJ exome

AF:

0.233

Gnomad EAS exome

AF:

0.390

Gnomad SAS exome

AF:

0.419

Gnomad FIN exome

AF:

0.225

Gnomad NFE exome

AF:

0.233

Gnomad OTH exome

AF:

0.270

GnomAD4 exome

AF:

0.248

AC:

331310

AN:

1333984

Hom.:

43410

Cov.:

AF XY:

0.253

AC XY:

164742

AN XY:

650630

show subpopulations

Gnomad4 AFR exome

AF:

0.0990

Gnomad4 AMR exome

AF:

0.304

Gnomad4 ASJ exome

AF:

0.231

Gnomad4 EAS exome

AF:

0.425

Gnomad4 SAS exome

AF:

0.417

Gnomad4 FIN exome

AF:

0.225

Gnomad4 NFE exome

AF:

0.235

Gnomad4 OTH exome

AF:

0.259

GnomAD4 genome

AF:

0.215

AC:

32707

AN:

152040

Hom.:

3940

Cov.:

AF XY:

0.221

AC XY:

16439

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.102

Gnomad4 AMR

AF:

0.274

Gnomad4 ASJ

AF:

0.224

Gnomad4 EAS

AF:

0.410

Gnomad4 SAS

AF:

0.430

Gnomad4 FIN

AF:

0.232

Gnomad4 NFE

AF:

0.237

Gnomad4 OTH

AF:

0.216

Alfa

AF:

0.230

Hom.:

2939

Bravo

AF:

0.209

Asia WGS

AF:

0.435

AC:

1512

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	May 13, 2021	- -
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

-0.91

CADD

Benign

0.24

DANN

Benign

0.47

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