NM_000033.4:c.1866-11C>A

Variant names:

• chrX-153743210-C-A
• rs782126372
• NM_000033.4:c.1866-11C>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_000033.4(ABCD1):​c.1866-11C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: ABCD1 NM_000033.4 intron
• Scores: Splicing: ADA: 0.9986
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.89
• Publications: 0 publications found

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]

PLXNB3-AS1 (HGNC:40454): (PLXNB3 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCD1	NM_000033.4	MANE Select	c.1866-11C>A		intron	N/A	NP_000024.2
	ABCD1	NM_001440747.1		c.2166-11C>A		intron	N/A	NP_001427676.1
	PLXNB3-AS1	NR_199693.1		n.90-4632G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCD1	ENST00000218104.6	TSL:1 MANE Select	c.1866-11C>A		intron	N/A	ENSP00000218104.3
	ABCD1	ENST00000862307.1		c.2166-11C>A		intron	N/A	ENSP00000532366.1
	ABCD1	ENST00000862306.1		c.2136-11C>A		intron	N/A	ENSP00000532365.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD2 exomes AF: 0.00 AC: 0 AN: 169098 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1093263 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 360427

African (AFR) AF: 0.00 AC: 0 AN: 26302

American (AMR) AF: 0.00 AC: 0 AN: 34925

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19287

East Asian (EAS) AF: 0.00 AC: 0 AN: 30096

South Asian (SAS) AF: 0.00 AC: 0 AN: 53252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39932

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2949

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 840722

Other (OTH) AF: 0.00 AC: 0 AN: 45798

GnomAD4 genome Cov.: 24

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Uncertain	24
DANN	Benign	0.70
PhyloP100		-1.9

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.83
SpliceAI score (max)		1.0		Details are displayed if max score is > 0.2
DS_AG_spliceai		1.0		Position offset: 2
DS_AL_spliceai		0.28		Position offset: 11

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

Other links and lift over

dbSNP: rs782126372; hg19: chrX-153008664;