chr19-35843517-G-A
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_004646.4(NPHS1):c.2289C>T(p.Val763Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0635 in 1,613,890 control chromosomes in the GnomAD database, including 10,206 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_004646.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -21 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NPHS1 | ENST00000378910.10 | c.2289C>T | p.Val763Val | synonymous_variant | Exon 17 of 29 | 1 | NM_004646.4 | ENSP00000368190.4 | ||
NPHS1 | ENST00000585400.1 | n.980C>T | non_coding_transcript_exon_variant | Exon 3 of 3 | 1 | |||||
NPHS1 | ENST00000353632.6 | c.2289C>T | p.Val763Val | synonymous_variant | Exon 17 of 28 | 5 | ENSP00000343634.5 |
Frequencies
GnomAD3 genomes AF: 0.161 AC: 24457AN: 152026Hom.: 4509 Cov.: 32
GnomAD3 exomes AF: 0.0788 AC: 19829AN: 251486Hom.: 2196 AF XY: 0.0717 AC XY: 9742AN XY: 135916
GnomAD4 exome AF: 0.0533 AC: 77898AN: 1461746Hom.: 5666 Cov.: 32 AF XY: 0.0523 AC XY: 38011AN XY: 727186
GnomAD4 genome AF: 0.161 AC: 24533AN: 152144Hom.: 4540 Cov.: 32 AF XY: 0.158 AC XY: 11740AN XY: 74396
ClinVar
Submissions by phenotype
Finnish congenital nephrotic syndrome Benign:5
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not provided Benign:4
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Variant summary: The NPHS1 c.2289C>T (p.Val763Val) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. 5/5 splice prediction tools predict no significant impact on normal splicing. This variant was found in 10368/121400 control chromosomes (1310 homozygotes), predominantly observed in the African subpopulation at a frequency of 0.4543533 (4728/10406). This frequency is about 135 times the estimated maximal expected allele frequency of a pathogenic NPHS1 variant (0.0033541), suggesting this is a benign common polymorphism found primarily in the populations of African origin. Therefore, this variant is classified as Benign. -
not specified Benign:2
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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 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