rs2229539

Variant names:

• chrX-153743743-G-A
• rs2229539
• NM_000033.4:c.*8G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-153743743-G-A
• chrX-153743743-G-C
• chrX-153743743-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000033.4(ABCD1):​c.*8G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000953 in 1,049,277 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples 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: not found (cov: 21)
  • Exomes 𝑓: 9.5e-7 (0 hom. 0 hem.)
• Consequence: ABCD1 NM_000033.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.382
• 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
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCD1	NM_000033.4	c.*8G>A		3_prime_UTR_variant	Exon 10 of 10	ENST00000218104.6	NP_000024.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCD1	ENST00000218104.6	c.*8G>A		3_prime_UTR_variant	Exon 10 of 10	1	NM_000033.4	ENSP00000218104.3
PLXNB3-AS1	ENST00000434284.1	n.72-5165C>T		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome AF: 9.53e-7 AC: 1 AN: 1049277 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 341921

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 25078

American (AMR) AF: 0.0000346 AC: 1 AN: 28885

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18607

East Asian (EAS) AF: 0.00 AC: 0 AN: 27524

South Asian (SAS) AF: 0.00 AC: 0 AN: 49926

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30009

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2856

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 822044

Other (OTH) AF: 0.00 AC: 0 AN: 44348

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.6
DANN	Benign	0.94
PhyloP100		-0.38

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: rs2229539; hg19: chrX-153009197;