Genetic Variant ABCD1:c.1082-33C>T (chrX-153736079-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_000033.4(ABCD1):c.1082-33C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00002 in 1,198,984 control chromosomes in the GnomAD database, including 1 homozygotes. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 24)

Exomes 𝑓: 0.000021 ( 1 hom. 8 hem. )

Consequence

ABCD1
NM_000033.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.95

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 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.0000212 (23/1086366) while in subpopulation MID AF = 0.00427 (15/3509). AF 95% confidence interval is 0.00263. There are 1 homozygotes in GnomAdExome4. There are 8 alleles in the male GnomAdExome4 subpopulation. Median coverage is 28. This position passed quality control check.

BS2

High AC in GnomAdExome4 at 23 XL,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000033.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ABCD1	NM_000033.4	MANE Select	c.1082-33C>T	intron	N/A	NP_000024.2
ABCD1	NM_001440747.1		c.1082-33C>T	intron	N/A	NP_001427676.1
PLXNB3-AS1	NR_199693.1		n.2589G>A	non_coding_transcript_exon	Exon 2 of 2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ABCD1	ENST00000218104.6	TSL:1 MANE Select	c.1082-33C>T	intron	N/A	ENSP00000218104.3	P33897
ABCD1	ENST00000862307.1		c.1082-33C>T	intron	N/A	ENSP00000532366.1
ABCD1	ENST00000862306.1		c.1082-33C>T	intron	N/A	ENSP00000532365.1

Frequencies

GnomAD3 genomes

AF:

0.00000888

AC:

AN:

112618

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000323

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

GnomAD2 exomes

AF:

0.0000175

AC:

AN:

171753

AF XY:

0.0000485

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000370

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000134

Gnomad OTH exome

AF:

0.000237

GnomAD4 exome

AF:

0.0000212

AC:

AN:

1086366

Hom.:

Cov.:

AF XY:

0.0000226

AC XY:

AN XY:

354094

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26158

American (AMR)

AF:

0.0000285

AC:

AN:

35056

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19252

East Asian (EAS)

AF:

0.00

AC:

AN:

30027

South Asian (SAS)

AF:

0.0000558

AC:

AN:

53767

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39202

Middle Eastern (MID)

AF:

0.00427

AC:

AN:

3509

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

833822

Other (OTH)

AF:

0.0000219

AC:

AN:

45573

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.606

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.00000888

AC:

AN:

112618

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34764

show subpopulations

African (AFR)

AF:

0.0000323

AC:

AN:

30981

American (AMR)

AF:

0.00

AC:

AN:

10653

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2650

East Asian (EAS)

AF:

0.00

AC:

AN:

3600

South Asian (SAS)

AF:

0.00

AC:

AN:

2767

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6229

Middle Eastern (MID)

AF:

0.00

AC:

AN:

237

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53302

Other (OTH)

AF:

0.00

AC:

AN:

1516

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000302

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

3.7

(source)

DANN

Benign

0.88

PhyloP100

1.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over