rs806104

chr1-5982874-G-Achr1-5982874-G-Cchr1-5982874-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015102.5(NPHP4):c.135+3281C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.609 in 152,050 control chromosomes in the GnomAD database, including 28,344 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.61 (28344 hom., cov: 33)
• Consequence: NPHP4 NM_015102.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.492

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPHP4	NM_015102.5	c.135+3281C>T		intron_variant		ENST00000378156.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPHP4	ENST00000378156.9	c.135+3281C>T		intron_variant		1	NM_015102.5	P2

Frequencies

GnomAD3 genomes AF: 0.609 AC: 92504 AN: 151932 Hom.: 28333 Cov.: 33

Gnomad AFR AF: 0.520

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.616

Gnomad ASJ AF: 0.640

Gnomad EAS AF: 0.759

Gnomad SAS AF: 0.629

Gnomad FIN AF: 0.681

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.636

Gnomad OTH AF: 0.614

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.609 AC: 92551 AN: 152050 Hom.: 28344 Cov.: 33 AF XY: 0.611 AC XY: 45413 AN XY: 74326

Gnomad4 AFR AF: 0.520

Gnomad4 AMR AF: 0.616

Gnomad4 ASJ AF: 0.640

Gnomad4 EAS AF: 0.760

Gnomad4 SAS AF: 0.628

Gnomad4 FIN AF: 0.681

Gnomad4 NFE AF: 0.636

Gnomad4 OTH AF: 0.617

Alfa AF: 0.610 Hom.: 11551

Bravo AF: 0.601

Asia WGS AF: 0.626 AC: 2180 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.25
Dann	Benign	0.78

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: rs806104; hg19: chr1-6042934; COSMIC: COSV65394043;