rs33950747
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM1BP6_Very_StrongBA1
The NM_004646.4(NPHS1):c.1223G>A(p.Arg408Gln) variant causes a missense change. The variant allele was found at a frequency of 0.061 in 1,614,022 control chromosomes in the GnomAD database, including 3,446 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_004646.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -14 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
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NPHS1 | ENST00000378910.10 | c.1223G>A | p.Arg408Gln | missense_variant | Exon 10 of 29 | 1 | NM_004646.4 | ENSP00000368190.4 | ||
NPHS1 | ENST00000353632.6 | c.1223G>A | p.Arg408Gln | missense_variant | Exon 10 of 28 | 5 | ENSP00000343634.5 | |||
NPHS1 | ENST00000592132.1 | n.230G>A | non_coding_transcript_exon_variant | Exon 3 of 4 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0434 AC: 6601AN: 152084Hom.: 192 Cov.: 32
GnomAD3 exomes AF: 0.0487 AC: 12251AN: 251370Hom.: 389 AF XY: 0.0483 AC XY: 6565AN XY: 135860
GnomAD4 exome AF: 0.0628 AC: 91858AN: 1461820Hom.: 3254 Cov.: 32 AF XY: 0.0614 AC XY: 44639AN XY: 727218
GnomAD4 genome AF: 0.0434 AC: 6599AN: 152202Hom.: 192 Cov.: 32 AF XY: 0.0431 AC XY: 3206AN XY: 74408
ClinVar
Submissions by phenotype
Finnish congenital nephrotic syndrome Benign:5
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This variant is interpreted as a Benign - Stand Alone, for Nephrotic syndrome, type 1, in Autosomal Recessive manner. The following ACMG Tag(s) were applied: BA1 => Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. -
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not provided Benign:4
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This variant is associated with the following publications: (PMID: 31216994, 27884173, 9915943, 21228398, 20981092, 20507940, 11726550, 24742477) -
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not specified Benign:2
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Atypical hemolytic-uremic syndrome Benign:1
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Congenital nephrotic syndrome Benign:1
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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at