rs398123101
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1
The NM_000033.4(ABCD1):c.1489-6del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00288 in 1,208,022 control chromosomes in the GnomAD database, including 103 homozygotes. There are 1,085 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0032 ( 13 hom., 119 hem., cov: 24)
Exomes 𝑓: 0.0028 ( 90 hom. 966 hem. )
Consequence
ABCD1
NM_000033.4 splice_polypyrimidine_tract, intron
NM_000033.4 splice_polypyrimidine_tract, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.254
Genes affected
ABCD1 (HGNC:61): (ATP binding cassette subfamily D member 1) The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the ALD subfamily, which is involved in peroxisomal import of fatty acids and/or fatty acyl-CoAs in the organelle. All known peroxisomal ABC transporters are half transporters which require a partner half transporter molecule to form a functional homodimeric or heterodimeric transporter. This peroxisomal membrane protein is likely involved in the peroxisomal transport or catabolism of very long chain fatty acids. Defects in this gene have been identified as the underlying cause of adrenoleukodystrophy, an X-chromosome recessively inherited demyelinating disorder of the nervous system. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP6
?
Variant X-153740082-GC-G is Benign according to our data. Variant chrX-153740082-GC-G is described in ClinVar as [Likely_benign]. Clinvar id is 92315.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-153740082-GC-G is described in Lovd as [Likely_benign].
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0827 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABCD1 | NM_000033.4 | c.1489-6del | splice_polypyrimidine_tract_variant, intron_variant | ENST00000218104.6 | |||
LOC124905226 | XR_007068350.1 | n.1465del | non_coding_transcript_exon_variant | 1/2 | |||
ABCD1 | XM_047441916.1 | c.1789-6del | splice_polypyrimidine_tract_variant, intron_variant | ||||
ABCD1 | XM_047441917.1 | c.1545-6del | splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABCD1 | ENST00000218104.6 | c.1489-6del | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000033.4 | P1 | |||
PLXNB3-AS1 | ENST00000434284.1 | n.72-1505del | intron_variant, non_coding_transcript_variant | 3 | |||||
ABCD1 | ENST00000443684.2 | n.492-6del | splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00321 AC: 362AN: 112875Hom.: 13 Cov.: 24 AF XY: 0.00337 AC XY: 118AN XY: 35023
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GnomAD3 exomes AF: 0.00753 AC: 1360AN: 180604Hom.: 40 AF XY: 0.00678 AC XY: 444AN XY: 65478
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GnomAD4 exome AF: 0.00284 AC: 3115AN: 1095093Hom.: 90 Cov.: 31 AF XY: 0.00268 AC XY: 966AN XY: 360949
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GnomAD4 genome ? AF: 0.00320 AC: 361AN: 112929Hom.: 13 Cov.: 24 AF XY: 0.00339 AC XY: 119AN XY: 35087
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:13
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Adrenoleukodystrophy Benign:6
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Dec 24, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Mar 21, 2022 | - - |
Benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
not provided Benign:4
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 19, 2020 | This variant is associated with the following publications: (PMID: 14556192, 24788897, 16996397, 22995991, 23835273) - |
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jul 07, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 03, 2013 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Computational scores
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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