rs372309740

chrX-153743609-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_000033.4(ABCD1):c.2112G>A(p.Ala704=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000209 in 1,192,550 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 89 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00045 (0 hom., 19 hem., cov: 24)
  • Exomes 𝑓: 0.00018 (0 hom. 70 hem.)
• Consequence: ABCD1 NM_000033.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -6.71

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

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant X-153743609-G-A is Benign according to our data. Variant chrX-153743609-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 528349.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-153743609-G-A is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-6.71 with no splicing effect.
• BS2: High Hemizygotes in GnomAd at 19 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCD1	NM_000033.4	c.2112G>A	p.Ala704=	synonymous_variant	10/10	ENST00000218104.6
ABCD1	XM_047441916.1	c.2412G>A	p.Ala804=	synonymous_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCD1	ENST00000218104.6	c.2112G>A	p.Ala704=	synonymous_variant	10/10	1	NM_000033.4	P1
PLXNB3-AS1	ENST00000434284.1	n.72-5031C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.000453 AC: 51 AN: 112707 Hom.: 0 Cov.: 24 AF XY: 0.000545 AC XY: 19 AN XY: 34885

Gnomad AFR AF: 0.0000644

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00195

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000357

Gnomad FIN AF: 0.000160

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000470

Gnomad OTH AF: 0.000657

GnomAD3 exomes AF: 0.000290 AC: 42 AN: 144873 Hom.: 0 AF XY: 0.000266 AC XY: 12 AN XY: 45077

Gnomad AFR exome AF: 0.000110

Gnomad AMR exome AF: 0.000292

Gnomad ASJ exome AF: 0.000149

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000127

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000511

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000183 AC: 198 AN: 1079791 Hom.: 0 Cov.: 37 AF XY: 0.000199 AC XY: 70 AN XY: 351939

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000182

Gnomad4 ASJ exome AF: 0.000105

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000773

Gnomad4 FIN exome AF: 0.0000259

Gnomad4 NFE exome AF: 0.000188

Gnomad4 OTH exome AF: 0.000375

GnomAD4 genome AF: 0.000452 AC: 51 AN: 112759 Hom.: 0 Cov.: 24 AF XY: 0.000544 AC XY: 19 AN XY: 34947

Gnomad4 AFR AF: 0.0000642

Gnomad4 AMR AF: 0.00195

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000358

Gnomad4 FIN AF: 0.000160

Gnomad4 NFE AF: 0.000470

Gnomad4 OTH AF: 0.000649

Alfa AF: 0.000304 Hom.: 1

Bravo AF: 0.000378

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Adrenoleukodystrophy Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

ABCD1: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	0.35
Dann	Benign	0.93

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: rs372309740; hg19: chrX-153009063;