rs41314153

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4BP6_Very_StrongBP7BA1

The NM_000033.4(ABCD1):c.1548G>A(p.Leu516Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,209,397 control chromosomes in the GnomAD database, including 5,009 homozygotes. There are 43,448 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.085 ( 358 hom., 2839 hem., cov: 24)

Exomes 𝑓: 0.11 ( 4651 hom. 40609 hem. )

Consequence

ABCD1
NM_000033.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:14

Conservation

PhyloP100: 0.211

Publications

15 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 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 -18 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.249).

BP6

Variant X-153740151-G-A is Benign according to our data. Variant chrX-153740151-G-A is described in ClinVar as Benign. ClinVar VariationId is 92316.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.211 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCD1	NM_000033.4 link	c.1548G>A	p.Leu516Leu	synonymous_variant	Exon 6 of 10	ENST00000218104.6	NP_000024.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
ABCD1	ENST00000218104.6 link	c.1548G>A	p.Leu516Leu	synonymous_variant	Exon 6 of 10	1	NM_000033.4	ENSP00000218104.3
ABCD1	ENST00000443684.2 link	n.551G>A		non_coding_transcript_exon_variant	Exon 5 of 6	3
PLXNB3-AS1	ENST00000434284.1 link	n.72-1573C>T		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.0852

AC:

9605

AN:

112700

Hom.:

358

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0465

Gnomad AMI

AF:

0.0218

Gnomad AMR

AF:

0.0574

Gnomad ASJ

AF:

0.0658

Gnomad EAS

AF:

0.0475

Gnomad SAS

AF:

0.143

Gnomad FIN

AF:

0.0965

Gnomad MID

AF:

0.0583

Gnomad NFE

AF:

0.114

Gnomad OTH

AF:

0.0791

GnomAD2 exomes

AF:

0.0953

AC:

17369

AN:

182332

AF XY:

0.102

show subpopulations

Gnomad AFR exome

AF:

0.0471

Gnomad AMR exome

AF:

0.0537

Gnomad ASJ exome

AF:

0.0691

Gnomad EAS exome

AF:

0.0475

Gnomad FIN exome

AF:

0.103

Gnomad NFE exome

AF:

0.112

Gnomad OTH exome

AF:

0.0962

GnomAD4 exome

AF:

0.110

AC:

120818

AN:

1096644

Hom.:

4651

Cov.:

AF XY:

0.112

AC XY:

40609

AN XY:

362150

show subpopulations

African (AFR)

AF:

0.0431

AC:

1137

AN:

26379

American (AMR)

AF:

0.0541

AC:

1903

AN:

35144

Ashkenazi Jewish (ASJ)

AF:

0.0676

AC:

1307

AN:

19339

East Asian (EAS)

AF:

0.0531

AC:

1602

AN:

30159

South Asian (SAS)

AF:

0.150

AC:

8132

AN:

54038

European-Finnish (FIN)

AF:

0.107

AC:

4340

AN:

40412

Middle Eastern (MID)

AF:

0.0830

AC:

343

AN:

4132

European-Non Finnish (NFE)

AF:

0.116

AC:

97416

AN:

841034

Other (OTH)

AF:

0.101

AC:

4638

AN:

46007

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

4603

9206

13810

18413

23016

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3634

7268

10902

14536

18170

<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:

0.0852

AC:

9608

AN:

112753

Hom.:

358

Cov.:

AF XY:

0.0813

AC XY:

2839

AN XY:

34933

show subpopulations

African (AFR)

AF:

0.0466

AC:

1452

AN:

31142

American (AMR)

AF:

0.0574

AC:

618

AN:

10774

Ashkenazi Jewish (ASJ)

AF:

0.0658

AC:

175

AN:

2660

East Asian (EAS)

AF:

0.0471

AC:

168

AN:

3566

South Asian (SAS)

AF:

0.145

AC:

401

AN:

2758

European-Finnish (FIN)

AF:

0.0965

AC:

601

AN:

6230

Middle Eastern (MID)

AF:

0.0457

AC:

AN:

219

European-Non Finnish (NFE)

AF:

0.114

AC:

6047

AN:

53180

Other (OTH)

AF:

0.0787

AC:

121

AN:

1537

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

330

660

991

1321

1651

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

122

244

366

488

610

<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:

0.0968

Hom.:

809

Bravo

AF:

0.0796

EpiCase

AF:

0.108

EpiControl

AF:

0.107

ClinVar

Significance: Benign

Submissions summary: Benign:14

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Mar 30, 2016

Eurofins Ntd Llc (ga)

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

- -

Feb 08, 2017

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This 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. -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Adrenoleukodystrophy

Benign:5

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jun 05, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This 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. -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: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

- -

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 16, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Mar 12, 2020

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

Nov 24, 2014

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

4.5

(source)

DANN

Benign

0.81

PhyloP100

0.21

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over