rs782693577

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

Scores

3
9
5

Clinical Significance

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

Conservation

PhyloP100: 2.80
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]

Genome browser will be placed here

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
ABCD1NM_000033.4 linkuse as main transcriptc.50G>A p.Arg17His missense_variant 1/10 ENST00000218104.6 NP_000024.2
ABCD1XM_047441916.1 linkuse as main transcriptc.50G>A p.Arg17His missense_variant 1/11 XP_047297872.1
ABCD1XM_047441917.1 linkuse as main transcriptc.50G>A p.Arg17His missense_variant 1/8 XP_047297873.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ABCD1ENST00000218104.6 linkuse as main transcriptc.50G>A p.Arg17His missense_variant 1/101 NM_000033.4 ENSP00000218104 P1

Frequencies

GnomAD3 genomes
AF:
0.000115
AC:
13
AN:
113002
Hom.:
0
Cov.:
25
AF XY:
0.000114
AC XY:
4
AN XY:
35148
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
GnomAD3 exomes
AF:
0.0000795
AC:
7
AN:
88054
Hom.:
0
AF XY:
0.0000768
AC XY:
2
AN XY:
26036
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 SAS 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
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000552
Gnomad4 EAS exome
AF:
0.000150
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000140
Gnomad4 OTH exome
AF:
0.0000687
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
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000244
Gnomad4 OTH
AF:
0.00
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
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 24, 2024- -
Likely benign, criteria provided, single submitterclinical testingGenome-Nilou LabNov 07, 2021- -
not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingARUP Laboratories, Molecular Genetics and Genomics, ARUP LaboratoriesApr 08, 2019- -
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsOct 11, 2016This 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 submitterclinical testingCeGaT Center for Human Genetics TuebingenAug 01, 2024ABCD1: 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
MutationTaster
Benign
0.51
D
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
Varity_R
0.35
gMVP
0.27

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: rs782693577; hg19: chrX-152990771; API