chrX-153740082-G-GC

Variant names:

• chrX-153740082-G-GC
• rs398123101
• NM_000033.4:c.1489-6dupC

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BS2

The NM_001440747.1(ABCD1):​c.1789-6dupC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000457 in 1,095,094 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000046 (0 hom. 1 hem.)
• Consequence: ABCD1 NM_001440747.1 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.254
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS2: High AC in GnomAdExome4 at 5 XL,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001440747.1. 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.1489-6dupC		splice_region intron	N/A	NP_000024.2
	ABCD1	NM_001440747.1		c.1789-6dupC		splice_region intron	N/A	NP_001427676.1
	PLXNB3-AS1	NR_199693.1		n.90-1505dupG		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCD1	ENST00000218104.6	TSL:1 MANE Select	c.1489-10_1489-9insC		intron	N/A	ENSP00000218104.3
	ABCD1	ENST00000862307.1		c.1789-10_1789-9insC		intron	N/A	ENSP00000532366.1
	ABCD1	ENST00000862306.1		c.1759-10_1759-9insC		intron	N/A	ENSP00000532365.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 0.00000457 AC: 5 AN: 1095094 Hom.: 0 Cov.: 31 AF XY: 0.00000277 AC XY: 1 AN XY: 360950

African (AFR) AF: 0.00 AC: 0 AN: 26364

American (AMR) AF: 0.00 AC: 0 AN: 35075

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19295

East Asian (EAS) AF: 0.00 AC: 0 AN: 30128

South Asian (SAS) AF: 0.00 AC: 0 AN: 53910

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40031

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4116

European-Non Finnish (NFE) AF: 0.00000595 AC: 5 AN: 840262

Other (OTH) AF: 0.00 AC: 0 AN: 45913

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.25

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

Other links and lift over

dbSNP: rs398123101; hg19: chrX-153005536;