rs114734921
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The ENST00000369569.6(AP4B1):āc.1723A>Gā(p.Ile575Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00562 in 1,614,224 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I575S) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000369569.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AP4B1 | NM_001253852.3 | c.1723A>G | p.Ile575Val | missense_variant | 9/10 | ENST00000369569.6 | NP_001240781.1 | |
AP4B1-AS1 | NR_125965.1 | n.415-2042T>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AP4B1 | ENST00000369569.6 | c.1723A>G | p.Ile575Val | missense_variant | 9/10 | 1 | NM_001253852.3 | ENSP00000358582 | P1 | |
AP4B1-AS1 | ENST00000419536.1 | n.247-2042T>C | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.00395 AC: 602AN: 152220Hom.: 10 Cov.: 33
GnomAD3 exomes AF: 0.00373 AC: 939AN: 251438Hom.: 5 AF XY: 0.00394 AC XY: 535AN XY: 135890
GnomAD4 exome AF: 0.00580 AC: 8476AN: 1461886Hom.: 40 Cov.: 31 AF XY: 0.00566 AC XY: 4113AN XY: 727242
GnomAD4 genome AF: 0.00395 AC: 601AN: 152338Hom.: 10 Cov.: 33 AF XY: 0.00365 AC XY: 272AN XY: 74494
ClinVar
Submissions by phenotype
Hereditary spastic paraplegia 47 Benign:4
Likely benign, criteria provided, single submitter | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | Jun 28, 2017 | - - |
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 27, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | May 10, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 15, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2024 | AP4B1: BP4, BS2 - |
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Dec 20, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Nov 18, 2015 | - - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 22, 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. - |
Hereditary spastic paraplegia Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Nov 03, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at