rs781146
Positions:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2
The NM_000181.4(GUSB):c.396+74A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00503 in 1,385,764 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.0033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0052 ( 25 hom. )
Consequence
GUSB
NM_000181.4 intron
NM_000181.4 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.447
Genes affected
GUSB (HGNC:4696): (glucuronidase beta) This gene encodes a hydrolase that degrades glycosaminoglycans, including heparan sulfate, dermatan sulfate, and chondroitin-4,6-sulfate. The enzyme forms a homotetramer that is localized to the lysosome. Mutations in this gene result in mucopolysaccharidosis type VII. Alternative splicing results in multiple transcript variants. There are many pseudogenes of this locus in the human genome.[provided by RefSeq, May 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00329 (501/152236) while in subpopulation NFE AF= 0.00544 (370/67998). AF 95% confidence interval is 0.00498. There are 0 homozygotes in gnomad4. There are 223 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome4 at 25 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GUSB | NM_000181.4 | c.396+74A>T | intron_variant | ENST00000304895.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GUSB | ENST00000304895.9 | c.396+74A>T | intron_variant | 1 | NM_000181.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00329 AC: 501AN: 152118Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00524 AC: 6467AN: 1233528Hom.: 25 AF XY: 0.00500 AC XY: 3079AN XY: 615618
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GnomAD4 genome ? AF: 0.00329 AC: 501AN: 152236Hom.: 0 Cov.: 32 AF XY: 0.00300 AC XY: 223AN XY: 74426
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ClinVar
Not reported inComputational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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