rs12406197
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_014625.4(NPHS2):c.-51G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 1,358,458 control chromosomes in the GnomAD database, including 47,137 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.24 ( 4506 hom., cov: 34)
Exomes 𝑓: 0.26 ( 42631 hom. )
Consequence
NPHS2
NM_014625.4 5_prime_UTR
NM_014625.4 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.14
Genes affected
NPHS2 (HGNC:13394): (NPHS2 stomatin family member, podocin) This gene encodes a protein that plays a role in the regulation of glomerular permeability. Mutations in this gene cause steroid-resistant nephrotic syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]
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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=-0.71).
BP6
?
Variant 1-179575915-C-A is Benign according to our data. Variant chr1-179575915-C-A is described in ClinVar as [Benign]. Clinvar id is 225144.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-179575915-C-A is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NPHS2 | NM_014625.4 | c.-51G>T | 5_prime_UTR_variant | 1/8 | ENST00000367615.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NPHS2 | ENST00000367615.9 | c.-51G>T | 5_prime_UTR_variant | 1/8 | 1 | NM_014625.4 | P1 | ||
NPHS2 | ENST00000367616.4 | c.-51G>T | 5_prime_UTR_variant | 1/7 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.237 AC: 35998AN: 152074Hom.: 4502 Cov.: 34
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GnomAD3 exomes AF: 0.255 AC: 5501AN: 21614Hom.: 753 AF XY: 0.254 AC XY: 3133AN XY: 12342
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GnomAD4 exome AF: 0.263 AC: 316772AN: 1206276Hom.: 42631 Cov.: 30 AF XY: 0.263 AC XY: 153097AN XY: 583210
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ClinVar
Significance: Benign
Submissions summary: Pathogenic:1Benign:10
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
Benign, no assertion criteria provided | clinical testing | Department of Pathology and Laboratory Medicine, Sinai Health System | - | - - |
Benign, criteria provided, single submitter | clinical testing | Mendelics | May 04, 2022 | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Nephrotic syndrome, type 2 Pathogenic:1Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Mar 06, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Likely pathogenic, flagged submission | clinical testing | Human Genetics Disease in Children – Taif University, Taif University | Jan 01, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | May 18, 2021 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 20, 2019 | This variant is associated with the following publications: (PMID: 16900088, 30793612) - |
NPHS2-related condition Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 23, 2021 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Focal segmental glomerulosclerosis Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Sep 27, 2022 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at