rs782693577
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2
The ENST00000218104.6(ABCD1):c.50G>A(p.Arg17His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000117 in 1,149,123 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 42 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00012 ( 0 hom., 4 hem., cov: 25)
Exomes 𝑓: 0.00012 ( 0 hom. 38 hem. )
Consequence
ABCD1
ENST00000218104.6 missense
ENST00000218104.6 missense
Scores
3
9
5
Clinical Significance
Conservation
PhyloP100: 2.80
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 -12 ACMG points.
BP6
Variant X-153725316-G-A is Benign according to our data. Variant chrX-153725316-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 583372.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High Hemizygotes in GnomAd4 at 4 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ABCD1 | NM_000033.4 | c.50G>A | p.Arg17His | missense_variant | 1/10 | ENST00000218104.6 | NP_000024.2 | |
ABCD1 | XM_047441916.1 | c.50G>A | p.Arg17His | missense_variant | 1/11 | XP_047297872.1 | ||
ABCD1 | XM_047441917.1 | c.50G>A | p.Arg17His | missense_variant | 1/8 | XP_047297873.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ABCD1 | ENST00000218104.6 | c.50G>A | p.Arg17His | missense_variant | 1/10 | 1 | NM_000033.4 | ENSP00000218104 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000115 AC: 13AN: 113002Hom.: 0 Cov.: 25 AF XY: 0.000114 AC XY: 4AN XY: 35148
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GnomAD3 exomes AF: 0.0000795 AC: 7AN: 88054Hom.: 0 AF XY: 0.0000768 AC XY: 2AN XY: 26036
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GnomAD4 exome AF: 0.000118 AC: 122AN: 1036121Hom.: 0 Cov.: 32 AF XY: 0.000114 AC XY: 38AN XY: 333847
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GnomAD4 genome AF: 0.000115 AC: 13AN: 113002Hom.: 0 Cov.: 25 AF XY: 0.000114 AC XY: 4AN XY: 35148
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ClinVar
Significance: Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Adrenoleukodystrophy Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 24, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Apr 08, 2019 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 11, 2016 | This alteration is classified as likely 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. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2024 | ABCD1: BS2 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Pathogenic
DEOGEN2
Pathogenic
D
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D
MetaSVM
Uncertain
D
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Loss of helix (P = 0.0076);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
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