rs11156606

Positions:

• chrX-153741041-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000033.4(ABCD1):​c.1780+322A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 112,144 control chromosomes in the GnomAD database, including 4,981 homozygotes. There are 8,590 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.26 (4981 hom., 8590 hem., cov: 24)
• Consequence: ABCD1 NM_000033.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.29

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]

LOC124905226 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant X-153741041-A-C is Benign according to our data. Variant chrX-153741041-A-C is described in ClinVar as [Benign]. Clinvar id is 1293829.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCD1	NM_000033.4	c.1780+322A>C		intron_variant		ENST00000218104.6	NP_000024.2
ABCD1	XM_047441916.1	c.2080+322A>C		intron_variant			XP_047297872.1
LOC124905226	XR_007068350.1	n.507T>G		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCD1	ENST00000218104.6	c.1780+322A>C		intron_variant		1	NM_000033.4	ENSP00000218104.3
PLXNB3-AS1	ENST00000434284.1	n.72-2463T>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.262 AC: 29371 AN: 112088 Hom.: 4970 Cov.: 24 AF XY: 0.249 AC XY: 8543 AN XY: 34282

Gnomad AFR AF: 0.640

Gnomad AMI AF: 0.0366

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.0694

Gnomad EAS AF: 0.0871

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.0917

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.222

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.262 AC: 29433 AN: 112144 Hom.: 4981 Cov.: 24 AF XY: 0.250 AC XY: 8590 AN XY: 34348

Gnomad4 AFR AF: 0.641

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.0694

Gnomad4 EAS AF: 0.0871

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.110

Gnomad4 NFE AF: 0.119

Gnomad4 OTH AF: 0.220

Alfa AF: 0.188 Hom.: 1565

Bravo AF: 0.281

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 06, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.5
DANN	Benign	0.35

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

LitVar

Other links and lift over

dbSNP: rs11156606; hg19: chrX-153006495;