1-179561279-G-GT
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2
The NM_014625.4(NPHS2):c.451+9dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00046 in 1,605,678 control chromosomes in the GnomAD database, including 9 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_014625.4 intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00216 AC: 328AN: 152066Hom.: 5 Cov.: 32
GnomAD3 exomes AF: 0.000621 AC: 156AN: 251324Hom.: 0 AF XY: 0.000523 AC XY: 71AN XY: 135826
GnomAD4 exome AF: 0.000283 AC: 412AN: 1453494Hom.: 4 Cov.: 29 AF XY: 0.000238 AC XY: 172AN XY: 723778
GnomAD4 genome AF: 0.00215 AC: 327AN: 152184Hom.: 5 Cov.: 32 AF XY: 0.00200 AC XY: 149AN XY: 74426
ClinVar
Submissions by phenotype
not specified Benign:3
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Variant summary: NPHS2 c.451+9dupA alters a non-conserved nucleotide located at a position not widely known to affect splicing. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00062 in 251324 control chromosomes, predominantly at a frequency of 0.0078 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 4.41 fold of the estimated maximal expected allele frequency for a pathogenic variant in NPHS2 causing Nephrotic Syndrome, Type 2 phenotype (0.0018). To our knowledge, no occurrence of c.451+9dupA in individuals affected with Nephrotic Syndrome, Type 2 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 260427). Based on the evidence outlined above, the variant was classified as benign. -
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Nephrotic syndrome, type 2 Benign:2
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Kidney disorder Benign:1
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not provided Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at