rs115555125

chr1-5873220-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_015102.5(NPHP4):c.3315+32G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00128 in 1,570,316 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0058 (11 hom., cov: 33)
  • Exomes 𝑓: 0.00080 (7 hom.)
• Consequence: NPHP4 NM_015102.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.442

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 1-5873220-C-T is Benign according to our data. Variant chr1-5873220-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 260555.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00576 (877/152326) while in subpopulation AFR AF= 0.0187 (777/41572). AF 95% confidence interval is 0.0176. There are 11 homozygotes in gnomad4. There are 418 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPHP4	NM_015102.5	c.3315+32G>A		intron_variant		ENST00000378156.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPHP4	ENST00000378156.9	c.3315+32G>A		intron_variant		1	NM_015102.5	P2

Frequencies

GnomAD3 genomes AF: 0.00576 AC: 876 AN: 152208 Hom.: 11 Cov.: 33

Gnomad AFR AF: 0.0187

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00327

Gnomad ASJ AF: 0.00518

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00670

GnomAD3 exomes AF: 0.00164 AC: 407 AN: 248122 Hom.: 3 AF XY: 0.00146 AC XY: 196 AN XY: 134678

Gnomad AFR exome AF: 0.0187

Gnomad AMR exome AF: 0.00102

Gnomad ASJ exome AF: 0.00329

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000656

Gnomad FIN exome AF: 0.000140

Gnomad NFE exome AF: 0.000169

Gnomad OTH exome AF: 0.00149

GnomAD4 exome AF: 0.000804 AC: 1140 AN: 1417990 Hom.: 7 Cov.: 25 AF XY: 0.000811 AC XY: 574 AN XY: 707908

Gnomad4 AFR exome AF: 0.0204

Gnomad4 AMR exome AF: 0.00110

Gnomad4 ASJ exome AF: 0.00294

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000528

Gnomad4 FIN exome AF: 0.000112

Gnomad4 NFE exome AF: 0.000150

Gnomad4 OTH exome AF: 0.00195

GnomAD4 genome AF: 0.00576 AC: 877 AN: 152326 Hom.: 11 Cov.: 33 AF XY: 0.00561 AC XY: 418 AN XY: 74480

Gnomad4 AFR AF: 0.0187

Gnomad4 AMR AF: 0.00327

Gnomad4 ASJ AF: 0.00518

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.00664

Alfa AF: 0.00398 Hom.: 1

Bravo AF: 0.00702

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.010
Dann	Benign	0.65

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

Other links and lift over

dbSNP: rs115555125; hg19: chr1-5933280;