rs739289
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_022081.6(HPS4):c.706+39G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.871 in 1,613,106 control chromosomes in the GnomAD database, including 616,054 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.82 ( 51970 hom., cov: 32)
Exomes 𝑓: 0.88 ( 564084 hom. )
Consequence
HPS4
NM_022081.6 intron
NM_022081.6 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -4.09
Genes affected
HPS4 (HGNC:15844): (HPS4 biogenesis of lysosomal organelles complex 3 subunit 2) This gene encodes a protein component of biogenesis of lysosome-related organelles complexes (BLOC). BLOC complexes are important for the formation of endosomal-lysosomal organelles such as melanosomes and platelet dense granules. Mutations in this gene result in subtype 4 of Hermansky-Pudlak syndrome, a form of albinism. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
?
Variant 22-26466187-C-A is Benign according to our data. Variant chr22-26466187-C-A is described in ClinVar as [Benign]. Clinvar id is 261537.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HPS4 | NM_022081.6 | c.706+39G>T | intron_variant | ENST00000398145.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HPS4 | ENST00000398145.7 | c.706+39G>T | intron_variant | 1 | NM_022081.6 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.821 AC: 124842AN: 152054Hom.: 51963 Cov.: 32
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GnomAD3 exomes AF: 0.844 AC: 212227AN: 251384Hom.: 90823 AF XY: 0.857 AC XY: 116503AN XY: 135882
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GnomAD4 exome AF: 0.877 AC: 1280845AN: 1460934Hom.: 564084 Cov.: 37 AF XY: 0.880 AC XY: 639402AN XY: 726830
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GnomAD4 genome ? AF: 0.821 AC: 124898AN: 152172Hom.: 51970 Cov.: 32 AF XY: 0.822 AC XY: 61187AN XY: 74412
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 12, 2018 | - - |
Hermansky-Pudlak syndrome 4 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Aug 10, 2021 | - - |
Computational 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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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at