rs398123101

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chrX-153740082-GC-G
• chrX-153740082-GC-GCC

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001440747.1(ABCD1):​c.1789-6delC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00288 in 1,208,022 control chromosomes in the GnomAD database, including 103 homozygotes. There are 1,085 hemizygotes in GnomAD. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0032 (13 hom., 119 hem., cov: 24)
  • Exomes 𝑓: 0.0028 (90 hom. 966 hem.)
• Consequence: ABCD1 NM_001440747.1 splice_region, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:13
• Conservation: PhyloP100: 0.254
• Publications: 6 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: Benign. The variant received -16 ACMG points.

• BP6: Variant X-153740082-GC-G is Benign according to our data. Variant chrX-153740082-GC-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 92315.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0827 is higher than 0.05.

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.1489-6delC		splice_region intron	N/A	NP_000024.2
	ABCD1	NM_001440747.1		c.1789-6delC		splice_region intron	N/A	NP_001427676.1
	PLXNB3-AS1	NR_199693.1		n.90-1505delG		intron	N/A

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes AF: 0.00321 AC: 362 AN: 112875 Hom.: 13 Cov.: 24

Gnomad AFR AF: 0.000418

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000836

Gnomad ASJ AF: 0.00226

Gnomad EAS AF: 0.0906

Gnomad SAS AF: 0.00253

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000563

Gnomad OTH AF: 0.00132

GnomAD2 exomes AF: 0.00753 AC: 1360 AN: 180604 AF XY: 0.00678

Gnomad AFR exome AF: 0.000762

Gnomad AMR exome AF: 0.000331

Gnomad ASJ exome AF: 0.00138

Gnomad EAS exome AF: 0.0924

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000137

Gnomad OTH exome AF: 0.00472

GnomAD4 exome AF: 0.00284 AC: 3115 AN: 1095093 Hom.: 90 Cov.: 31 AF XY: 0.00268 AC XY: 966 AN XY: 360949

African (AFR) AF: 0.000417 AC: 11 AN: 26364

American (AMR) AF: 0.000314 AC: 11 AN: 35075

Ashkenazi Jewish (ASJ) AF: 0.00114 AC: 22 AN: 19295

East Asian (EAS) AF: 0.0861 AC: 2595 AN: 30128

South Asian (SAS) AF: 0.000649 AC: 35 AN: 53910

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40030

Middle Eastern (MID) AF: 0.000243 AC: 1 AN: 4116

European-Non Finnish (NFE) AF: 0.0000666 AC: 56 AN: 840262

Other (OTH) AF: 0.00836 AC: 384 AN: 45913

GnomAD4 genome AF: 0.00320 AC: 361 AN: 112929 Hom.: 13 Cov.: 24 AF XY: 0.00339 AC XY: 119 AN XY: 35087

African (AFR) AF: 0.000417 AC: 13 AN: 31202

American (AMR) AF: 0.000835 AC: 9 AN: 10774

Ashkenazi Jewish (ASJ) AF: 0.00226 AC: 6 AN: 2656

East Asian (EAS) AF: 0.0909 AC: 322 AN: 3542

South Asian (SAS) AF: 0.00217 AC: 6 AN: 2764

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6248

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 217

European-Non Finnish (NFE) AF: 0.0000563 AC: 3 AN: 53303

Other (OTH) AF: 0.00130 AC: 2 AN: 1538

Alfa AF: 0.00165 Hom.: 5

Bravo AF: 0.00428

Asia WGS AF: 0.0430 AC: 109 AN: 2521

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	Adrenoleukodystrophy (6)
-	-	4	not provided (4)
-	-	3	not specified (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.25
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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;