chrX-153740082-GC-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000033.4(ABCD1):c.1489-6delC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00288 in 1,208,022 control chromosomes in the GnomAD database, including 103 homozygotes. There are 1,085 hemizygotes in GnomAD. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0032 ( 13 hom., 119 hem., cov: 24)

Exomes 𝑓: 0.0028 ( 90 hom. 966 hem. )

Consequence

ABCD1
NM_000033.4 splice_region, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: 0.254

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 links:

LOC124905226 (HGNC:):

LOC124905226 links:

PLXNB3-AS1 (HGNC:40454): (PLXNB3 antisense RNA 1)

PLXNB3-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant X-153740082-GC-G is Benign according to our data. Variant chrX-153740082-GC-G is described in ClinVar as [Likely_benign]. Clinvar id is 92315.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-153740082-GC-G is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ABCD1	NM_000033.4 link	c.1489-6delC	splice_region_variant, intron_variant	Intron 5 of 9	ENST00000218104.6	NP_000024.2	P33897
ABCD1	XM_047441916.1 link	c.1789-6delC	splice_region_variant, intron_variant	Intron 6 of 10		XP_047297872.1
ABCD1	XM_047441917.1 link	c.1545-6delC	splice_region_variant, intron_variant	Intron 6 of 7		XP_047297873.1
LOC124905226	XR_007068350.1 link	n.1465delG	non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ABCD1	ENST00000218104.6 link	c.1489-9delC	intron_variant	Intron 5 of 9	1	NM_000033.4	ENSP00000218104.3	P33897
PLXNB3-AS1	ENST00000434284.1 link	n.72-1505delG	intron_variant	Intron 1 of 2	3
ABCD1	ENST00000443684.2 link	n.492-9delC	intron_variant	Intron 4 of 5	3

Frequencies

GnomAD3 genomes

AF:

0.00321

AC:

362

AN:

112875

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000418

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000836

Gnomad ASJ

AF:

0.00226

Gnomad EAS

AF:

0.0906

Gnomad SAS

AF:

0.00253

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000563

Gnomad OTH

AF:

0.00132

GnomAD2 exomes

AF:

0.00753

AC:

1360

AN:

180604

AF XY:

0.00678

show subpopulations

Gnomad AFR exome

AF:

0.000762

Gnomad AMR exome

AF:

0.000331

Gnomad ASJ exome

AF:

0.00138

Gnomad EAS exome

AF:

0.0924

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000137

Gnomad OTH exome

AF:

0.00472

GnomAD4 exome

AF:

0.00284

AC:

3115

AN:

1095093

Hom.:

Cov.:

AF XY:

0.00268

AC XY:

966

AN XY:

360949

show subpopulations

Gnomad4 AFR exome

AF:

0.000417

AC:

AN:

26364

Gnomad4 AMR exome

AF:

0.000314

AC:

AN:

35075

Gnomad4 ASJ exome

AF:

0.00114

AC:

AN:

19295

Gnomad4 EAS exome

AF:

0.0861

AC:

2595

AN:

30128

Gnomad4 SAS exome

AF:

0.000649

AC:

AN:

53910

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

40030

Gnomad4 NFE exome

AF:

0.0000666

AC:

AN:

840262

Gnomad4 Remaining exome

AF:

0.00836

AC:

384

AN:

45913

Heterozygous variant carriers

136

273

409

546

682

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

104

156

208

260

<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:

0.00320

AC:

361

AN:

112929

Hom.:

Cov.:

AF XY:

0.00339

AC XY:

119

AN XY:

35087

show subpopulations

Gnomad4 AFR

AF:

0.000417

AC:

0.00041664

AN:

0.00041664

Gnomad4 AMR

AF:

0.000835

AC:

0.000835344

AN:

0.000835344

Gnomad4 ASJ

AF:

0.00226

AC:

0.00225904

AN:

0.00225904

Gnomad4 EAS

AF:

0.0909

AC:

0.0909091

AN:

0.0909091

Gnomad4 SAS

AF:

0.00217

AC:

0.00217077

AN:

0.00217077

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.0000563

AC:

0.000056282

AN:

0.000056282

Gnomad4 OTH

AF:

0.00130

AC:

0.00130039

AN:

0.00130039

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

<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:

0.00165

Hom.:

Bravo

AF:

0.00428

Asia WGS

AF:

0.0430

AC:

109

AN:

2521

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Adrenoleukodystrophy

Benign:6

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 07, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 21, 2022

Fulgent Genetics, Fulgent Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 24, 2019

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:4

Clinical Genetics, Academic Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jun 19, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 14556192, 24788897, 16996397, 22995991, 23835273) -

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not specified

Benign:3

Jun 03, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 07, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Mutation Taster

=99/1

polymorphism (auto)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over