Genetic Variant NM_000033.4:c.1082-19C>G (chrX-153736093-C-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PP3_ModerateBP6_ModerateBS2

The NM_000033.4(ABCD1):c.1082-19C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000237 in 1,206,446 control chromosomes in the GnomAD database, including 1 homozygotes. There are 103 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00028 ( 1 hom., 12 hem., cov: 24)

Exomes 𝑓: 0.00023 ( 0 hom. 91 hem. )

Consequence

ABCD1
NM_000033.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.155

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: Likely_benign. The variant received -4 ACMG points.

PP3

Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

BP6

Variant X-153736093-C-G is Benign according to our data. Variant chrX-153736093-C-G is described in ClinVar as [Benign]. Clinvar id is 1545912.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 32 XL,AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCD1	NM_000033.4 link	c.1082-19C>G		intron_variant	Intron 2 of 9	ENST00000218104.6	NP_000024.2	P33897

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ABCD1	ENST00000218104.6 link	c.1082-19C>G	intron_variant	Intron 2 of 9	1	NM_000033.4	ENSP00000218104.3	P33897
PLXNB3-AS1	ENST00000434284.1 link	n.581-134G>C	intron_variant	Intron 2 of 2	3
ABCD1	ENST00000443684.2 link	n.85-19C>G	intron_variant	Intron 1 of 5	3

Frequencies

GnomAD3 genomes

AF:

0.000284

AC:

AN:

112547

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000323

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000187

Gnomad ASJ

AF:

0.00529

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000244

Gnomad OTH

AF:

0.00132

GnomAD2 exomes

AF:

0.000464

AC:

AN:

178780

AF XY:

0.000529

show subpopulations

Gnomad AFR exome

AF:

0.0000810

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00561

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000445

Gnomad OTH exome

AF:

0.00137

GnomAD4 exome

AF:

0.000232

AC:

254

AN:

1093899

Hom.:

Cov.:

AF XY:

0.000253

AC XY:

AN XY:

360061

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26333

American (AMR)

AF:

0.00

AC:

AN:

35176

Ashkenazi Jewish (ASJ)

AF:

0.00610

AC:

118

AN:

19349

East Asian (EAS)

AF:

0.00

AC:

AN:

30156

South Asian (SAS)

AF:

0.00

AC:

AN:

54029

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39691

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3901

European-Non Finnish (NFE)

AF:

0.000138

AC:

116

AN:

839326

Other (OTH)

AF:

0.000435

AC:

AN:

45938

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.561

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000284

AC:

AN:

112547

Hom.:

Cov.:

AF XY:

0.000346

AC XY:

AN XY:

34707

show subpopulations

African (AFR)

AF:

0.0000323

AC:

AN:

30945

American (AMR)

AF:

0.000187

AC:

AN:

10703

Ashkenazi Jewish (ASJ)

AF:

0.00529

AC:

AN:

2646

East Asian (EAS)

AF:

0.00

AC:

AN:

3609

South Asian (SAS)

AF:

0.00

AC:

AN:

2763

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6193

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.000244

AC:

AN:

53247

Other (OTH)

AF:

0.00132

AC:

AN:

1519

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00104

Hom.:

Bravo

AF:

0.000264

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Adrenoleukodystrophy

Benign:1

Jan 22, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Uncertain

(source)

DANN

Benign

0.48

PhyloP100

-0.15

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.99

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.99

Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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NM_000033.4:c.1082-19C>G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over