chrX-153725867-G-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000033.4(ABCD1):c.601G>A(p.Val201Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000108 in 1,210,757 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 29 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00048 ( 0 hom., 9 hem., cov: 26)

Exomes 𝑓: 0.000070 ( 0 hom. 20 hem. )

Consequence

ABCD1
NM_000033.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.454

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.056189775).

BP6

Variant X-153725867-G-A is Benign according to our data. Variant chrX-153725867-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 585357.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000476 (54/113553) while in subpopulation AFR AF= 0.00137 (43/31387). AF 95% confidence interval is 0.00104. There are 0 homozygotes in gnomad4. There are 9 alleles in male gnomad4 subpopulation. Median coverage is 26. This position pass quality control queck.

BS2

High Hemizygotes in GnomAd4 at 9 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCD1	NM_000033.4 link	c.601G>A	p.Val201Met	missense_variant	Exon 1 of 10	ENST00000218104.6	NP_000024.2	P33897
ABCD1	XM_047441916.1 link	c.601G>A	p.Val201Met	missense_variant	Exon 1 of 11		XP_047297872.1
ABCD1	XM_047441917.1 link	c.601G>A	p.Val201Met	missense_variant	Exon 1 of 8		XP_047297873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCD1	ENST00000218104.6 link	c.601G>A	p.Val201Met	missense_variant	Exon 1 of 10	1	NM_000033.4	ENSP00000218104.3		P33897
ABCD1	ENST00000370129.4 link	c.46G>A	p.Val16Met	missense_variant	Exon 1 of 2	2		ENSP00000359147.3		A6NEP8

Frequencies

GnomAD3 genomes

AF:

0.000476

AC:

AN:

113500

Hom.:

Cov.:

AF XY:

0.000253

AC XY:

AN XY:

35636

show subpopulations

Gnomad AFR

AF:

0.00137

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000920

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:

0.0000187

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000148

AC:

AN:

181930

Hom.:

AF XY:

0.000149

AC XY:

AN XY:

66918

show subpopulations

Gnomad AFR exome

AF:

0.00168

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:

0.0000370

Gnomad OTH exome

AF:

0.000443

GnomAD4 exome

AF:

0.0000702

AC:

AN:

1097204

Hom.:

Cov.:

AF XY:

0.0000551

AC XY:

AN XY:

362994

show subpopulations

Gnomad4 AFR exome

AF:

0.00193

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000119

Gnomad4 OTH exome

AF:

0.000325

GnomAD4 genome

AF:

0.000476

AC:

AN:

113553

Hom.:

Cov.:

AF XY:

0.000252

AC XY:

AN XY:

35699

show subpopulations

Gnomad4 AFR

AF:

0.00137

Gnomad4 AMR

AF:

0.000919

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000187

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000389

Hom.:

Bravo

AF:

0.000480

ESP6500AA

AF:

0.00156

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.000165

AC:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Adrenoleukodystrophy

Benign:2

Nov 07, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 24, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

May 05, 2018

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ABCD1: BS2 -

Inborn genetic diseases

Benign:1

May 28, 2017

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. -

ABCD1-related disorder

Benign:1

May 06, 2023

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.090

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.93

D;D

FATHMM_MKL

Benign

0.15

LIST_S2

Uncertain

0.87

D;D

M_CAP

Pathogenic

0.62

MetaRNN

Benign

0.056

T;T

MetaSVM

Pathogenic

1.3

MutationAssessor

Uncertain

2.7

M;.

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-1.8

N;N

REVEL

Uncertain

0.42

Sift

Uncertain

0.011

D;D

Sift4G

Uncertain

0.0030

D;D

Polyphen

0.23

B;.

Vest4

0.099

MVP

0.97

MPC

0.88

ClinPred

0.026

GERP RS

1.3

Varity_R

0.20

gMVP

0.80

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