rs782693577

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2

The NM_000033.4(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
NM_000033.4 missense

Scores

3
9
5

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 2.80

Publications

3 publications found
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]
ABCD1 Gene-Disease associations (from GenCC):
  • adrenoleukodystrophy
    Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P
  • X-linked cerebral adrenoleukodystrophy
    Inheritance: XL Classification: DEFINITIVE, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Orphanet
  • hereditary spastic paraplegia
    Inheritance: XL Classification: STRONG Submitted by: Genomics England PanelApp
  • Hirschsprung disease
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • adrenomyeloneuropathy
    Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 AC in GnomAd4 at 13 XL,AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ABCD1NM_000033.4 linkc.50G>A p.Arg17His missense_variant Exon 1 of 10 ENST00000218104.6 NP_000024.2 P33897
ABCD1NM_001440747.1 linkc.50G>A p.Arg17His missense_variant Exon 1 of 11 NP_001427676.1
ABCD1XM_047441917.1 linkc.50G>A p.Arg17His missense_variant Exon 1 of 8 XP_047297873.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ABCD1ENST00000218104.6 linkc.50G>A p.Arg17His missense_variant Exon 1 of 10 1 NM_000033.4 ENSP00000218104.3 P33897

Frequencies

GnomAD3 genomes
AF:
0.000115
AC:
13
AN:
113002
Hom.:
0
Cov.:
25
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000244
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000795
AC:
7
AN:
88054
AF XY:
0.0000768
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000217
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000118
AC:
122
AN:
1036121
Hom.:
0
Cov.:
32
AF XY:
0.000114
AC XY:
38
AN XY:
333847
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
24297
American (AMR)
AF:
0.00
AC:
0
AN:
26685
Ashkenazi Jewish (ASJ)
AF:
0.0000552
AC:
1
AN:
18107
East Asian (EAS)
AF:
0.000150
AC:
4
AN:
26729
South Asian (SAS)
AF:
0.00
AC:
0
AN:
48592
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
31927
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
3030
European-Non Finnish (NFE)
AF:
0.000140
AC:
114
AN:
813071
Other (OTH)
AF:
0.0000687
AC:
3
AN:
43683
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.496
Heterozygous variant carriers
0
4
9
13
18
22
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
4
8
12
16
20
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.000115
AC:
13
AN:
113002
Hom.:
0
Cov.:
25
AF XY:
0.000114
AC XY:
4
AN XY:
35148
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
31176
American (AMR)
AF:
0.00
AC:
0
AN:
10874
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
2654
East Asian (EAS)
AF:
0.00
AC:
0
AN:
3558
South Asian (SAS)
AF:
0.00
AC:
0
AN:
2833
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
6276
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
240
European-Non Finnish (NFE)
AF:
0.000244
AC:
13
AN:
53189
Other (OTH)
AF:
0.00
AC:
0
AN:
1524
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.458
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.000102
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000346
AC:
1
ExAC
AF:
0.0000642
AC:
4

ClinVar

Significance: Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Adrenoleukodystrophy Benign:2
Nov 07, 2021
Genome-Nilou Lab
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Jan 20, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

not specified Benign:1
Apr 08, 2019
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Inborn genetic diseases Benign:1
Oct 11, 2016
Ambry Genetics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

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
Aug 01, 2024
CeGaT Center for Human Genetics Tuebingen
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

ABCD1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Uncertain
0.14
D
BayesDel_noAF
Uncertain
-0.040
CADD
Uncertain
24
DANN
Pathogenic
1.0
DEOGEN2
Pathogenic
0.80
D
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Benign
0.85
D
M_CAP
Pathogenic
0.41
D
MetaRNN
Uncertain
0.61
D
MetaSVM
Uncertain
0.49
D
MutationAssessor
Benign
0.81
L
PhyloP100
2.8
PrimateAI
Uncertain
0.73
T
PROVEAN
Benign
-2.2
N
REVEL
Uncertain
0.48
Sift
Uncertain
0.015
D
Sift4G
Uncertain
0.015
D
Polyphen
0.99
D
Vest4
0.40
MutPred
0.43
Loss of helix (P = 0.0076);
MVP
0.96
MPC
1.4
ClinPred
0.20
T
GERP RS
5.1
PromoterAI
-0.055
Neutral
Varity_R
0.35
gMVP
0.27
Mutation Taster
=84/16
polymorphism

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

Other links and lift over

dbSNP: rs782693577; hg19: chrX-152990771; API