rs189953957
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The ENST00000398145.7(HPS4):c.1956-32T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.01 in 1,611,714 control chromosomes in the GnomAD database, including 110 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0074 ( 8 hom., cov: 32)
Exomes 𝑓: 0.010 ( 102 hom. )
Consequence
HPS4
ENST00000398145.7 intron
ENST00000398145.7 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -4.33
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=-0.92).
BP6
Variant 22-26453436-A-G is Benign according to our data. Variant chr22-26453436-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 261534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00735 (1120/152338) while in subpopulation NFE AF= 0.0112 (760/68036). AF 95% confidence interval is 0.0105. There are 8 homozygotes in gnomad4. There are 571 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 8 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HPS4 | NM_022081.6 | c.1956-32T>C | intron_variant | ENST00000398145.7 | NP_071364.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HPS4 | ENST00000398145.7 | c.1956-32T>C | intron_variant | 1 | NM_022081.6 | ENSP00000381213 | P2 |
Frequencies
GnomAD3 genomes AF: 0.00735 AC: 1119AN: 152220Hom.: 8 Cov.: 32
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GnomAD3 exomes AF: 0.00811 AC: 2039AN: 251356Hom.: 11 AF XY: 0.00838 AC XY: 1138AN XY: 135860
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GnomAD4 exome AF: 0.0103 AC: 15057AN: 1459376Hom.: 102 Cov.: 30 AF XY: 0.0102 AC XY: 7427AN XY: 726122
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GnomAD4 genome AF: 0.00735 AC: 1120AN: 152338Hom.: 8 Cov.: 32 AF XY: 0.00766 AC XY: 571AN XY: 74496
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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