rs4806213
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_004646.4(NPHS1):āc.3230A>Gā(p.Asn1077Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 1,602,890 control chromosomes in the GnomAD database, including 8,826 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Consequence
NM_004646.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NPHS1 | NM_004646.4 | c.3230A>G | p.Asn1077Ser | missense_variant | 24/29 | ENST00000378910.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NPHS1 | ENST00000378910.10 | c.3230A>G | p.Asn1077Ser | missense_variant | 24/29 | 1 | NM_004646.4 | P2 | |
NPHS1 | ENST00000353632.6 | c.3167-199A>G | intron_variant | 5 | A2 |
Frequencies
GnomAD3 genomes AF: 0.105 AC: 15946AN: 151246Hom.: 880 Cov.: 31
GnomAD3 exomes AF: 0.0970 AC: 22452AN: 231452Hom.: 1141 AF XY: 0.0977 AC XY: 12240AN XY: 125268
GnomAD4 exome AF: 0.101 AC: 146169AN: 1451526Hom.: 7945 Cov.: 34 AF XY: 0.101 AC XY: 72803AN XY: 721406
GnomAD4 genome AF: 0.106 AC: 15982AN: 151364Hom.: 881 Cov.: 31 AF XY: 0.106 AC XY: 7870AN XY: 73920
ClinVar
Submissions by phenotype
Finnish congenital nephrotic syndrome Benign:4
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jun 10, 2021 | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | Jul 20, 2015 | - - |
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 29, 2019 | This variant is associated with the following publications: (PMID: 31216994, 28476686, 9915943, 15086927, 27884173, 12495287, 21228398, 20981092, 20507940) - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Aug 16, 2017 | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 24, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Focal segmental glomerulosclerosis Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Sep 27, 2022 | - - |
Congenital nephrotic syndrome Benign:1
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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at