rs752693324
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The ENST00000261842.10(AP4E1):c.3117C>T(p.Asp1039=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000293 in 1,612,486 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00031 ( 11 hom. )
Consequence
AP4E1
ENST00000261842.10 synonymous
ENST00000261842.10 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.99
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 -19 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.35).
BP6
Variant 15-51001047-C-T is Benign according to our data. Variant chr15-51001047-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 434237.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=1.99 with no splicing effect.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000105 (16/152216) while in subpopulation SAS AF= 0.00311 (15/4826). AF 95% confidence interval is 0.00192. There are 0 homozygotes in gnomad4. There are 13 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 11 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AP4E1 | NM_007347.5 | c.3117C>T | p.Asp1039= | synonymous_variant | 20/21 | ENST00000261842.10 | NP_031373.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AP4E1 | ENST00000261842.10 | c.3117C>T | p.Asp1039= | synonymous_variant | 20/21 | 1 | NM_007347.5 | ENSP00000261842 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000105 AC: 16AN: 152100Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000567 AC: 142AN: 250484Hom.: 3 AF XY: 0.000775 AC XY: 105AN XY: 135410
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GnomAD4 exome AF: 0.000313 AC: 457AN: 1460270Hom.: 11 Cov.: 31 AF XY: 0.000450 AC XY: 327AN XY: 726504
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GnomAD4 genome AF: 0.000105 AC: 16AN: 152216Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13AN XY: 74412
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Mar 14, 2016 | - - |
Spastic paraplegia Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 22, 2024 | - - |
Hereditary spastic paraplegia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Nov 18, 2020 | - - |
Stuttering, familial persistent, 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Dec 05, 2021 | - - |
Hereditary spastic paraplegia 51 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Dec 05, 2021 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
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