rs183021839
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_000033.4(ABCD1):āc.38A>Cā(p.Asn13Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00264 in 1,146,578 control chromosomes in the GnomAD database, including 6 homozygotes. There are 979 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Consequence
NM_000033.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABCD1 | NM_000033.4 | c.38A>C | p.Asn13Thr | missense_variant | 1/10 | ENST00000218104.6 | |
ABCD1 | XM_047441916.1 | c.38A>C | p.Asn13Thr | missense_variant | 1/11 | ||
ABCD1 | XM_047441917.1 | c.38A>C | p.Asn13Thr | missense_variant | 1/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABCD1 | ENST00000218104.6 | c.38A>C | p.Asn13Thr | missense_variant | 1/10 | 1 | NM_000033.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00223 AC: 251AN: 112804Hom.: 0 Cov.: 25 AF XY: 0.00257 AC XY: 90AN XY: 35004
GnomAD3 exomes AF: 0.00203 AC: 174AN: 85534Hom.: 1 AF XY: 0.00169 AC XY: 41AN XY: 24244
GnomAD4 exome AF: 0.00268 AC: 2772AN: 1033723Hom.: 6 Cov.: 32 AF XY: 0.00267 AC XY: 889AN XY: 332361
GnomAD4 genome ? AF: 0.00222 AC: 251AN: 112855Hom.: 0 Cov.: 25 AF XY: 0.00257 AC XY: 90AN XY: 35065
ClinVar
Submissions by phenotype
not provided Benign:5
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 13, 2021 | - - |
Adrenoleukodystrophy Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 14, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jan 11, 2024 | Variant summary: ABCD1 c.38A>C (p.Asn13Thr) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0026 in 1146578 control chromosomes in the gnomAD database (v4), including 979 hemizygotes and 6 homozygotes, strongly suggesting the variant is a benign polymorphism. To our knowledge, no occurrences of c.38A>C with strong evidence for causality have been reported in individuals affected with Adrenoleukodystrophy. At least one publication reports experimental evidence evaluating an impact on protein function and showed no damaging effect of this variant (Dvorakova_2001). The following publication has been ascertained in the context of this evaluation (PMID: 11438993). ClinVar contains an entry for this variant (Variation ID: 368044). Based on the evidence outlined above, the variant was classified as benign. - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 09, 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
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at