rs3747129
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_022081.6(HPS4):c.706+151C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 1,567,474 control chromosomes in the GnomAD database, including 22,302 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.12 ( 1643 hom., cov: 32)
Exomes 𝑓: 0.16 ( 20659 hom. )
Consequence
HPS4
NM_022081.6 intron
NM_022081.6 intron
Scores
1
6
Clinical Significance
Conservation
PhyloP100: -0.0160
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 -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_addAF=-0.833905).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HPS4 | NM_022081.6 | c.706+151C>T | intron_variant | ENST00000398145.7 | NP_071364.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HPS4 | ENST00000398145.7 | c.706+151C>T | intron_variant | 1 | NM_022081.6 | ENSP00000381213 | P2 |
Frequencies
GnomAD3 genomes AF: 0.124 AC: 18821AN: 152036Hom.: 1638 Cov.: 32
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GnomAD3 exomes AF: 0.173 AC: 33094AN: 191268Hom.: 3600 AF XY: 0.188 AC XY: 19282AN XY: 102368
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GnomAD4 exome AF: 0.160 AC: 226005AN: 1415320Hom.: 20659 Cov.: 31 AF XY: 0.167 AC XY: 116803AN XY: 701058
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GnomAD4 genome AF: 0.124 AC: 18837AN: 152154Hom.: 1643 Cov.: 32 AF XY: 0.130 AC XY: 9690AN XY: 74364
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 12, 2018 | - - |
Computational scores
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Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
MutationTaster
Benign
P;P;P;P
GERP RS
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