rs78870657
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS1
The NM_007347.5(AP4E1):c.1566C>G(p.Ser522=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000589 in 1,612,216 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00039 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00061 ( 2 hom. )
Consequence
AP4E1
NM_007347.5 synonymous
NM_007347.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.133
Genes affected
AP4E1 (HGNC:573): (adaptor related protein complex 4 subunit epsilon 1) This gene encodes a member of the adaptor complexes large subunit protein family. These proteins are components of the heterotetrameric adaptor protein complexes, which play important roles in the secretory and endocytic pathways by mediating vesicle formation and sorting of integral membrane proteins. The encoded protein is a large subunit of adaptor protein complex-4, which is associated with both clathrin- and nonclathrin-coated vesicles. Disruption of this gene may be associated with cerebral palsy. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.41).
BP6
?
Variant 15-50958509-C-G is Benign according to our data. Variant chr15-50958509-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 390912.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-50958509-C-G is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=0.133 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000394 (60/152224) while in subpopulation SAS AF= 0.000829 (4/4828). AF 95% confidence interval is 0.000405. There are 0 homozygotes in gnomad4. There are 24 alleles in male gnomad4 subpopulation. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AP4E1 | NM_007347.5 | c.1566C>G | p.Ser522= | synonymous_variant | 14/21 | ENST00000261842.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AP4E1 | ENST00000261842.10 | c.1566C>G | p.Ser522= | synonymous_variant | 14/21 | 1 | NM_007347.5 | P1 | |
AP4E1 | ENST00000560508.1 | c.1341C>G | p.Ser447= | synonymous_variant | 14/21 | 1 | |||
AP4E1 | ENST00000558439.5 | c.*690C>G | 3_prime_UTR_variant, NMD_transcript_variant | 14/21 | 1 | ||||
AP4E1 | ENST00000561393.5 | c.*610C>G | 3_prime_UTR_variant, NMD_transcript_variant | 13/20 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.000394 AC: 60AN: 152106Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000548 AC: 136AN: 248084Hom.: 0 AF XY: 0.000514 AC XY: 69AN XY: 134146
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GnomAD4 exome AF: 0.000610 AC: 890AN: 1459992Hom.: 2 Cov.: 31 AF XY: 0.000622 AC XY: 452AN XY: 726250
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ClinVar
Significance: Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Dec 15, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 18, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Spastic paraplegia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 10, 2023 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2023 | AP4E1: BP4, BP7 - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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Dann
Benign
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