rs41302176

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000033.4(ABCD1):c.901-16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0112 in 1,210,356 control chromosomes in the GnomAD database, including 87 homozygotes. There are 4,322 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 0.0081 ( 5 hom., 252 hem., cov: 23)

Exomes 𝑓: 0.012 ( 82 hom. 4070 hem. )

Consequence

ABCD1
NM_000033.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.0110

Publications

0 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 Gene-Disease associations (from GenCC):

adrenoleukodystrophy
Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P
X-linked cerebral adrenoleukodystrophy
Inheritance: XL Classification: DEFINITIVE, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Orphanet
hereditary spastic paraplegia
Inheritance: XL Classification: STRONG Submitted by: Genomics England PanelApp
Hirschsprung disease
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
adrenomyeloneuropathy
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ABCD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant X-153729216-C-T is Benign according to our data. Variant chrX-153729216-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 92329.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0081 (913/112729) while in subpopulation NFE AF = 0.0131 (698/53238). AF 95% confidence interval is 0.0123. There are 5 homozygotes in GnomAd4. There are 252 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.

BS2

High AC in GnomAd4 at 913 XL,AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ABCD1	NM_000033.4 link	c.901-16C>T	intron_variant	Intron 1 of 9	ENST00000218104.6	NP_000024.2	P33897
ABCD1	NM_001440747.1 link	c.901-16C>T	intron_variant	Intron 1 of 10		NP_001427676.1
ABCD1	XM_047441917.1 link	c.901-16C>T	intron_variant	Intron 1 of 7		XP_047297873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCD1	ENST00000218104.6 link	c.901-16C>T		intron_variant	Intron 1 of 9	1	NM_000033.4	ENSP00000218104.3		P33897
ABCD1	ENST00000370129.4 link	c.346-16C>T		intron_variant	Intron 1 of 1	2		ENSP00000359147.3		A6NEP8

Frequencies

GnomAD3 genomes

AF:

0.00809

AC:

912

AN:

112675

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00171

Gnomad AMI

AF:

0.0501

Gnomad AMR

AF:

0.00317

Gnomad ASJ

AF:

0.00714

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000361

Gnomad FIN

AF:

0.00995

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0131

Gnomad OTH

AF:

0.00790

GnomAD2 exomes

AF:

0.00765

AC:

1395

AN:

182246

AF XY:

0.00734

show subpopulations

Gnomad AFR exome

AF:

0.00190

Gnomad AMR exome

AF:

0.00201

Gnomad ASJ exome

AF:

0.00589

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0106

Gnomad NFE exome

AF:

0.0131

Gnomad OTH exome

AF:

0.00687

GnomAD4 exome

AF:

0.0115

AC:

12676

AN:

1097627

Hom.:

Cov.:

AF XY:

0.0112

AC XY:

4070

AN XY:

363051

show subpopulations

African (AFR)

AF:

0.00189

AC:

AN:

26394

American (AMR)

AF:

0.00233

AC:

AN:

35203

Ashkenazi Jewish (ASJ)

AF:

0.00738

AC:

143

AN:

19384

East Asian (EAS)

AF:

0.0000331

AC:

AN:

30203

South Asian (SAS)

AF:

0.000702

AC:

AN:

54128

European-Finnish (FIN)

AF:

0.0111

AC:

446

AN:

40284

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4129

European-Non Finnish (NFE)

AF:

0.0137

AC:

11501

AN:

841816

Other (OTH)

AF:

0.00900

AC:

415

AN:

46086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

450

899

1349

1798

2248

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

442

884

1326

1768

2210

<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:

0.00810

AC:

913

AN:

112729

Hom.:

Cov.:

AF XY:

0.00723

AC XY:

252

AN XY:

34865

show subpopulations

African (AFR)

AF:

0.00170

AC:

AN:

31091

American (AMR)

AF:

0.00317

AC:

AN:

10740

Ashkenazi Jewish (ASJ)

AF:

0.00714

AC:

AN:

2660

East Asian (EAS)

AF:

0.00

AC:

AN:

3576

South Asian (SAS)

AF:

0.000362

AC:

AN:

2759

European-Finnish (FIN)

AF:

0.00995

AC:

AN:

6229

Middle Eastern (MID)

AF:

0.00

AC:

AN:

219

European-Non Finnish (NFE)

AF:

0.0131

AC:

698

AN:

53238

Other (OTH)

AF:

0.00780

AC:

AN:

1538

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

104

139

174

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

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:

0.0102

Hom.:

Bravo

AF:

0.00741

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 03, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 03, 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. -

Adrenoleukodystrophy

Benign:3

Nov 07, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 29, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Clinical Genetics, Academic Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.8

(source)

DANN

Benign

0.74

PhyloP100

0.011

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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