Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_001253852.3(AP4B1):c.402A>T(p.Ser134Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,614,052 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. S134S) has been classified as Benign.
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]
AP4B1 Gene-Disease associations (from GenCC):
AP-4 deficiency syndrome
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Our verdict: Likely_benign. The variant received -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 1-113901822-T-A is Benign according to our data. Variant chr1-113901822-T-A is described in CliVar as Likely_benign. Clinvar id is 761146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-113901822-T-A is described in CliVar as Likely_benign. Clinvar id is 761146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-113901822-T-A is described in CliVar as Likely_benign. Clinvar id is 761146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-113901822-T-A is described in CliVar as Likely_benign. Clinvar id is 761146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-113901822-T-A is described in CliVar as Likely_benign. Clinvar id is 761146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-113901822-T-A is described in CliVar as Likely_benign. Clinvar id is 761146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-113901822-T-A is described in CliVar as Likely_benign. Clinvar id is 761146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-113901822-T-A is described in CliVar as Likely_benign. Clinvar id is 761146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-113901822-T-A is described in CliVar as Likely_benign. Clinvar id is 761146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-113901822-T-A is described in CliVar as Likely_benign. Clinvar id is 761146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-113901822-T-A is described in CliVar as Likely_benign. Clinvar id is 761146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-113901822-T-A is described in CliVar as Likely_benign. Clinvar id is 761146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-113901822-T-A is described in CliVar as Likely_benign. Clinvar id is 761146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-113901822-T-A is described in CliVar as Likely_benign. Clinvar id is 761146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-113901822-T-A is described in CliVar as Likely_benign. Clinvar id is 761146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-113901822-T-A is described in CliVar as Likely_benign. Clinvar id is 761146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-113901822-T-A is described in CliVar as Likely_benign. Clinvar id is 761146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-113901822-T-A is described in CliVar as Likely_benign. Clinvar id is 761146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-113901822-T-A is described in CliVar as Likely_benign. Clinvar id is 761146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-113901822-T-A is described in CliVar as Likely_benign. Clinvar id is 761146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-113901822-T-A is described in CliVar as Likely_benign. Clinvar id is 761146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-113901822-T-A is described in CliVar as Likely_benign. Clinvar id is 761146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-113901822-T-A is described in CliVar as Likely_benign. Clinvar id is 761146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-113901822-T-A is described in CliVar as Likely_benign. Clinvar id is 761146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-113901822-T-A is described in CliVar as Likely_benign. Clinvar id is 761146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-113901822-T-A is described in CliVar as Likely_benign. Clinvar id is 761146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-113901822-T-A is described in CliVar as Likely_benign. Clinvar id is 761146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-113901822-T-A is described in CliVar as Likely_benign. Clinvar id is 761146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-113901822-T-A is described in CliVar as Likely_benign. Clinvar id is 761146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-113901822-T-A is described in CliVar as Likely_benign. Clinvar id is 761146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-113901822-T-A is described in CliVar as Likely_benign. Clinvar id is 761146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-113901822-T-A is described in CliVar as Likely_benign. Clinvar id is 761146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-113901822-T-A is described in CliVar as Likely_benign. Clinvar id is 761146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-113901822-T-A is described in CliVar as Likely_benign. Clinvar id is 761146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-113901822-T-A is described in CliVar as Likely_benign. Clinvar id is 761146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-113901822-T-A is described in CliVar as Likely_benign. Clinvar id is 761146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-113901822-T-A is described in CliVar as Likely_benign. Clinvar id is 761146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-113901822-T-A is described in CliVar as Likely_benign. Clinvar id is 761146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-113901822-T-A is described in CliVar as Likely_benign. Clinvar id is 761146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-113901822-T-A is described in CliVar as Likely_benign. Clinvar id is 761146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-113901822-T-A is described in CliVar as Likely_benign. Clinvar id is 761146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-113901822-T-A is described in CliVar as Likely_benign. Clinvar id is 761146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-113901822-T-A is described in CliVar as Likely_benign. Clinvar id is 761146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-113901822-T-A is described in CliVar as Likely_benign. Clinvar id is 761146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-113901822-T-A is described in CliVar as Likely_benign. Clinvar id is 761146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-113901822-T-A is described in CliVar as Likely_benign. Clinvar id is 761146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-113901822-T-A is described in CliVar as Likely_benign. Clinvar id is 761146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-113901822-T-A is described in CliVar as Likely_benign. Clinvar id is 761146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-113901822-T-A is described in CliVar as Likely_benign. Clinvar id is 761146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-113901822-T-A is described in CliVar as Likely_benign. Clinvar id is 761146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-113901822-T-A is described in CliVar as Likely_benign. Clinvar id is 761146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-113901822-T-A is described in CliVar as Likely_benign. Clinvar id is 761146.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-113901822-T-A is described in CliVar as Likely_benign. Clinvar id is 761146.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.468 with no splicing effect.