rs117872964
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001253852.3(AP4B1):āc.69A>Gā(p.Gln23=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00102 in 1,613,602 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.00089 ( 3 hom., cov: 33)
Exomes š: 0.0010 ( 37 hom. )
Consequence
AP4B1
NM_001253852.3 synonymous
NM_001253852.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.42
Genes affected
AP4B1 (HGNC:572): (adaptor related protein complex 4 subunit beta 1) This gene encodes a subunit of a heterotetrameric adapter-like complex 4 that is involved in targeting proteins from the trans-Golgi network to the endosomal-lysosomal system. Mutations in this gene are associated with cerebral palsy spastic quadriplegic type 5 (CPSQ5) disorder. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]
DCLRE1B (HGNC:17641): (DNA cross-link repair 1B) DNA interstrand cross-links prevent strand separation, thereby physically blocking transcription, replication, and segregation of DNA. DCLRE1B is one of several evolutionarily conserved genes involved in repair of interstrand cross-links (Dronkert et al., 2000 [PubMed 10848582]).[supplied by OMIM, Mar 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP6
?
Variant 1-113904649-T-C is Benign according to our data. Variant chr1-113904649-T-C is described in ClinVar as [Benign]. Clinvar id is 157726.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-113904649-T-C is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=2.42 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000887 (135/152284) while in subpopulation EAS AF= 0.0258 (133/5164). AF 95% confidence interval is 0.0222. There are 3 homozygotes in gnomad4. There are 86 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AP4B1 | NM_001253852.3 | c.69A>G | p.Gln23= | synonymous_variant | 1/10 | ENST00000369569.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AP4B1 | ENST00000369569.6 | c.69A>G | p.Gln23= | synonymous_variant | 1/10 | 1 | NM_001253852.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000887 AC: 135AN: 152166Hom.: 3 Cov.: 33
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GnomAD3 exomes AF: 0.00170 AC: 428AN: 251488Hom.: 5 AF XY: 0.00163 AC XY: 222AN XY: 135920
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GnomAD4 exome AF: 0.00103 AC: 1506AN: 1461318Hom.: 37 Cov.: 31 AF XY: 0.000999 AC XY: 726AN XY: 726982
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GnomAD4 genome ? AF: 0.000887 AC: 135AN: 152284Hom.: 3 Cov.: 33 AF XY: 0.00115 AC XY: 86AN XY: 74460
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Hereditary spastic paraplegia 47 Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 10, 2024 | - - |
not specified Benign:1
Likely benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | - | - - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 20, 2016 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
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