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rs2229539

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_000033.4(ABCD1):c.*8G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.71 ( 19982 hom., 22195 hem., cov: 21)
Exomes 𝑓: 0.66 ( 154206 hom. 227087 hem. )
Failed GnomAD Quality Control

Consequence

ABCD1
NM_000033.4 3_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -0.382
Variant links:
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]
PLXNB3-AS1 (HGNC:40454): (PLXNB3 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BP6
Variant X-153743743-G-C is Benign according to our data. Variant chrX-153743743-G-C is described in ClinVar as [Benign]. Clinvar id is 92313.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-153743743-G-C is described in Lovd as [Benign]. Variant chrX-153743743-G-C is described in Lovd as [Likely_benign].
BS2
High Homozygotes in GnomAd at 19973 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ABCD1NM_000033.4 linkuse as main transcriptc.*8G>C 3_prime_UTR_variant 10/10 ENST00000218104.6
ABCD1XM_047441916.1 linkuse as main transcriptc.*8G>C 3_prime_UTR_variant 11/11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ABCD1ENST00000218104.6 linkuse as main transcriptc.*8G>C 3_prime_UTR_variant 10/101 NM_000033.4 P1
PLXNB3-AS1ENST00000434284.1 linkuse as main transcriptn.72-5165C>G intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.708
AC:
77353
AN:
109318
Hom.:
19973
Cov.:
21
AF XY:
0.699
AC XY:
22133
AN XY:
31644
show subpopulations
Gnomad AFR
AF:
0.843
Gnomad AMI
AF:
0.555
Gnomad AMR
AF:
0.704
Gnomad ASJ
AF:
0.589
Gnomad EAS
AF:
0.614
Gnomad SAS
AF:
0.765
Gnomad FIN
AF:
0.638
Gnomad MID
AF:
0.665
Gnomad NFE
AF:
0.650
Gnomad OTH
AF:
0.681
GnomAD3 exomes
AF:
0.673
AC:
70334
AN:
104522
Hom.:
15937
AF XY:
0.674
AC XY:
23445
AN XY:
34766
show subpopulations
Gnomad AFR exome
AF:
0.847
Gnomad AMR exome
AF:
0.696
Gnomad ASJ exome
AF:
0.595
Gnomad EAS exome
AF:
0.577
Gnomad SAS exome
AF:
0.764
Gnomad FIN exome
AF:
0.657
Gnomad NFE exome
AF:
0.641
Gnomad OTH exome
AF:
0.664
GnomAD4 exome
Data not reliable, filtered out with message: InbreedingCoeff
AF:
0.660
AC:
692706
AN:
1048760
Hom.:
154206
Cov.:
35
AF XY:
0.664
AC XY:
227087
AN XY:
341782
show subpopulations
Gnomad4 AFR exome
AF:
0.853
Gnomad4 AMR exome
AF:
0.702
Gnomad4 ASJ exome
AF:
0.599
Gnomad4 EAS exome
AF:
0.649
Gnomad4 SAS exome
AF:
0.765
Gnomad4 FIN exome
AF:
0.662
Gnomad4 NFE exome
AF:
0.648
Gnomad4 OTH exome
AF:
0.672
GnomAD4 genome
Data not reliable, filtered out with message: InbreedingCoeff
AF:
0.708
AC:
77420
AN:
109369
Hom.:
19982
Cov.:
21
AF XY:
0.700
AC XY:
22195
AN XY:
31705
show subpopulations
Gnomad4 AFR
AF:
0.844
Gnomad4 AMR
AF:
0.705
Gnomad4 ASJ
AF:
0.589
Gnomad4 EAS
AF:
0.614
Gnomad4 SAS
AF:
0.766
Gnomad4 FIN
AF:
0.638
Gnomad4 NFE
AF:
0.650
Gnomad4 OTH
AF:
0.683
Alfa
AF:
0.669
Hom.:
7845
Bravo
AF:
0.719

ClinVar

Significance: Benign
Submissions summary: Benign:11
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:5
Benign, no assertion criteria providedclinical testingJoint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+-- -
Benign, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)May 25, 2018- -
Benign, no assertion criteria providedclinical testingClinical Genetics, Academic Medical Center-- -
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Benign, criteria provided, single submitterclinical testingGeneDxMar 07, 2016This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Adrenoleukodystrophy Benign:3
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 14, 2021- -
Benign, no assertion criteria providedclinical testingNatera, Inc.Sep 16, 2020- -
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
not provided Benign:2
Benign, no assertion criteria providedclinical testingMayo Clinic Laboratories, Mayo ClinicOct 22, 2015- -
Benign, criteria provided, single submitterclinical testingARUP Laboratories, Molecular Genetics and Genomics, ARUP LaboratoriesSep 17, 2021- -
History of neurodevelopmental disorder Benign:1
Benign, criteria provided, single submitterclinical testingAmbry GeneticsAug 27, 2015This alteration is classified as benign based on a combination of the following: 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
Cadd
Benign
2.3
Dann
Benign
0.53

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2229539; hg19: chrX-153009197; API