Genetic Variant ABCD1:c.1082-7T>G (chrX-153736105-T-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_000033.4(ABCD1):c.1082-7T>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., 0 hem., cov: 25)

Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

ABCD1
NM_000033.4 splice_region, intron

Scores

Splicing: ADA: 0.002068

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.972

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant X-153736105-T-G is Benign according to our data. Variant chrX-153736105-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 3020310.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCD1	NM_000033.4 link	c.1082-7T>G		splice_region_variant, 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.1082-7T>G	splice_region_variant, intron_variant	Intron 2 of 9	1	NM_000033.4	ENSP00000218104.3	P33897
PLXNB3-AS1	ENST00000434284.1 link	n.581-146A>C	intron_variant	Intron 2 of 2	3
ABCD1	ENST00000443684.2 link	n.85-7T>G	splice_region_variant, intron_variant	Intron 1 of 5	3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

108690

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

878017

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

275749

African (AFR)

AF:

0.00

AC:

AN:

20585

American (AMR)

AF:

0.00

AC:

AN:

31318

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14412

East Asian (EAS)

AF:

0.00

AC:

AN:

18431

South Asian (SAS)

AF:

0.00

AC:

AN:

51068

European-Finnish (FIN)

AF:

0.00

AC:

AN:

27305

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3209

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

677296

Other (OTH)

AF:

0.00

AC:

AN:

34393

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

108765

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

32953

African (AFR)

AF:

0.00

AC:

AN:

30264

American (AMR)

AF:

0.00

AC:

AN:

10414

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2605

East Asian (EAS)

AF:

0.00

AC:

AN:

3123

South Asian (SAS)

AF:

0.00

AC:

AN:

2309

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5481

Middle Eastern (MID)

AF:

0.00

AC:

AN:

213

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

52192

Other (OTH)

AF:

0.00

AC:

AN:

1501

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Adrenoleukodystrophy

Benign:1

Jan 10, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely 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

-0.84

CADD

Benign

6.3

(source)

DANN

Benign

0.62

PhyloP100

0.97

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0021

dbscSNV1_RF

Benign

0.098

SpliceAI score (max)

0.12

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

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over