rs41314153

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_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

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 made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant X-153740151-G-A is Benign according to our data. Variant chrX-153740151-G-A is described in ClinVar as [Benign]. Clinvar id is 92316.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-153740151-G-A is described in Lovd as [Benign]. Variant chrX-153740151-G-A is described in Lovd as [Likely_benign].

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	P33897
ABCD1	XM_047441917.1 link	c.1604G>A	p.Cys535Tyr	missense_variant	Exon 7 of 8		XP_047297873.1
ABCD1	XM_047441916.1 link	c.1848G>A	p.Leu616Leu	synonymous_variant	Exon 7 of 11		XP_047297872.1
LOC124905226	XR_007068350.1 link	n.1397C>T		non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ABCD1	ENST00000218104.6 link	c.1548G>A	p.Leu516Leu	synonymous_variant	Exon 6 of 10	1	NM_000033.4	ENSP00000218104.3	P33897
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.:

AF XY:

0.0812

AC XY:

2832

AN XY:

34870

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

GnomAD3 exomes

AF:

0.0953

AC:

17369

AN:

182332

Hom.:

578

AF XY:

0.102

AC XY:

6845

AN XY:

66896

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 SAS exome

AF:

0.154

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

Gnomad4 AFR exome

AF:

0.0431

Gnomad4 AMR exome

AF:

0.0541

Gnomad4 ASJ exome

AF:

0.0676

Gnomad4 EAS exome

AF:

0.0531

Gnomad4 SAS exome

AF:

0.150

Gnomad4 FIN exome

AF:

0.107

Gnomad4 NFE exome

AF:

0.116

Gnomad4 OTH exome

AF:

0.101

GnomAD4 genome

AF:

0.0852

AC:

9608

AN:

112753

Hom.:

358

Cov.:

AF XY:

0.0813

AC XY:

2839

AN XY:

34933

show subpopulations

Gnomad4 AFR

AF:

0.0466

Gnomad4 AMR

AF:

0.0574

Gnomad4 ASJ

AF:

0.0658

Gnomad4 EAS

AF:

0.0471

Gnomad4 SAS

AF:

0.145

Gnomad4 FIN

AF:

0.0965

Gnomad4 NFE

AF:

0.114

Gnomad4 OTH

AF:

0.0787

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

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

- -

Mar 30, 2016

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Adrenoleukodystrophy

Benign:5

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. -

Jun 05, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

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

Dec 16, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

DANN

Benign

0.81

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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.

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