rs41314153

Variant names:

• chrX-153740151-G-A
• rs41314153
• NM_000033.4:c.1548G>A

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4 BP6_Very_Strong BP7 BA1

The NM_000033.4(ABCD1):​c.1548G>A​(p.Leu516Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,209,397 control chromosomes in the GnomAD database, including 5,009 homozygotes. There are 43,448 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.085 (358 hom., 2839 hem., cov: 24)
  • Exomes 𝑓: 0.11 (4651 hom. 40609 hem.)
• Consequence: ABCD1 NM_000033.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:14
• Conservation: PhyloP100: 0.211
• Publications: 15 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.249).
• BP6: Variant X-153740151-G-A is Benign according to our data. Variant chrX-153740151-G-A is described in ClinVar as Benign. ClinVar VariationId is 92316.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.211 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000033.4. 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.1548G>A	p.Leu516Leu	synonymous	Exon 6 of 10	NP_000024.2
	ABCD1	NM_001440747.1		c.1848G>A	p.Leu616Leu	synonymous	Exon 7 of 11	NP_001427676.1
	PLXNB3-AS1	NR_199693.1		n.90-1573C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCD1	ENST00000218104.6	TSL:1 MANE Select	c.1548G>A	p.Leu516Leu	synonymous	Exon 6 of 10	ENSP00000218104.3	P33897
	ABCD1	ENST00000862307.1		c.1848G>A	p.Leu616Leu	synonymous	Exon 7 of 11	ENSP00000532366.1
	ABCD1	ENST00000862306.1		c.1818G>A	p.Leu606Leu	synonymous	Exon 7 of 11	ENSP00000532365.1

Frequencies

GnomAD3 genomes AF: 0.0852 AC: 9605 AN: 112700 Hom.: 358 Cov.: 24

Gnomad AFR AF: 0.0465

Gnomad AMI AF: 0.0218

Gnomad AMR AF: 0.0574

Gnomad ASJ AF: 0.0658

Gnomad EAS AF: 0.0475

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.0965

Gnomad MID AF: 0.0583

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.0791

GnomAD2 exomes AF: 0.0953 AC: 17369 AN: 182332 AF XY: 0.102

Gnomad AFR exome AF: 0.0471

Gnomad AMR exome AF: 0.0537

Gnomad ASJ exome AF: 0.0691

Gnomad EAS exome AF: 0.0475

Gnomad FIN exome AF: 0.103

Gnomad NFE exome AF: 0.112

Gnomad OTH exome AF: 0.0962

GnomAD4 exome AF: 0.110 AC: 120818 AN: 1096644 Hom.: 4651 Cov.: 32 AF XY: 0.112 AC XY: 40609 AN XY: 362150

African (AFR) AF: 0.0431 AC: 1137 AN: 26379

American (AMR) AF: 0.0541 AC: 1903 AN: 35144

Ashkenazi Jewish (ASJ) AF: 0.0676 AC: 1307 AN: 19339

East Asian (EAS) AF: 0.0531 AC: 1602 AN: 30159

South Asian (SAS) AF: 0.150 AC: 8132 AN: 54038

European-Finnish (FIN) AF: 0.107 AC: 4340 AN: 40412

Middle Eastern (MID) AF: 0.0830 AC: 343 AN: 4132

European-Non Finnish (NFE) AF: 0.116 AC: 97416 AN: 841034

Other (OTH) AF: 0.101 AC: 4638 AN: 46007

GnomAD4 genome AF: 0.0852 AC: 9608 AN: 112753 Hom.: 358 Cov.: 24 AF XY: 0.0813 AC XY: 2839 AN XY: 34933

African (AFR) AF: 0.0466 AC: 1452 AN: 31142

American (AMR) AF: 0.0574 AC: 618 AN: 10774

Ashkenazi Jewish (ASJ) AF: 0.0658 AC: 175 AN: 2660

East Asian (EAS) AF: 0.0471 AC: 168 AN: 3566

South Asian (SAS) AF: 0.145 AC: 401 AN: 2758

European-Finnish (FIN) AF: 0.0965 AC: 601 AN: 6230

Middle Eastern (MID) AF: 0.0457 AC: 10 AN: 219

European-Non Finnish (NFE) AF: 0.114 AC: 6047 AN: 53180

Other (OTH) AF: 0.0787 AC: 121 AN: 1537

Alfa AF: 0.0968 Hom.: 809

Bravo AF: 0.0796

EpiCase AF: 0.108

EpiControl AF: 0.107

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	Adrenoleukodystrophy (5)
-	-	5	not specified (5)
-	-	3	not provided (3)
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	4.5
DANN	Benign	0.81
PhyloP100		0.21
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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: rs41314153; hg19: chrX-153005605; COSMIC: COSV54383338;