chrX-153743457-C-T

Variant names:

• chrX-153743457-C-T
• rs4898368
• NM_000033.4:c.1992-32C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_001440747.1(ABCD1):​c.2292-32C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.59 (13955 hom., 19421 hem., cov: 22)
  • Exomes 𝑓: 0.64 (147059 hom. 227195 hem.)
  • Failed GnomAD Quality Control
• Consequence: ABCD1 NM_001440747.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.08
• Publications: 10 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant X-153743457-C-T is Benign according to our data. Variant chrX-153743457-C-T is described in ClinVar as Benign. ClinVar VariationId is 439347.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCD1	NM_000033.4	MANE Select	c.1992-32C>T		intron	N/A	NP_000024.2
	ABCD1	NM_001440747.1		c.2292-32C>T		intron	N/A	NP_001427676.1
	PLXNB3-AS1	NR_199693.1		n.90-4879G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCD1	ENST00000218104.6	TSL:1 MANE Select	c.1992-32C>T		intron	N/A	ENSP00000218104.3
	ABCD1	ENST00000862307.1		c.2292-32C>T		intron	N/A	ENSP00000532366.1
	ABCD1	ENST00000862306.1		c.2262-32C>T		intron	N/A	ENSP00000532365.1

Frequencies

GnomAD3 genomes AF: 0.594 AC: 65532 AN: 110381 Hom.: 13954 Cov.: 22

Gnomad AFR AF: 0.486

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.651

Gnomad ASJ AF: 0.577

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.632

Gnomad MID AF: 0.637

Gnomad NFE AF: 0.634

Gnomad OTH AF: 0.581

GnomAD2 exomes AF: 0.628 AC: 97817 AN: 155788 AF XY: 0.629

Gnomad AFR exome AF: 0.476

Gnomad AMR exome AF: 0.670

Gnomad ASJ exome AF: 0.588

Gnomad EAS exome AF: 0.535

Gnomad FIN exome AF: 0.646

Gnomad NFE exome AF: 0.620

Gnomad OTH exome AF: 0.639

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.636 AC: 689259 AN: 1083863 Hom.: 147059 Cov.: 41 AF XY: 0.642 AC XY: 227195 AN XY: 354053

African (AFR) AF: 0.484 AC: 12666 AN: 26172

American (AMR) AF: 0.673 AC: 22674 AN: 33669

Ashkenazi Jewish (ASJ) AF: 0.589 AC: 11255 AN: 19098

East Asian (EAS) AF: 0.601 AC: 17867 AN: 29707

South Asian (SAS) AF: 0.763 AC: 40099 AN: 52571

European-Finnish (FIN) AF: 0.650 AC: 25555 AN: 39339

Middle Eastern (MID) AF: 0.627 AC: 1803 AN: 2874

European-Non Finnish (NFE) AF: 0.633 AC: 528553 AN: 834979

Other (OTH) AF: 0.633 AC: 28787 AN: 45454

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.594 AC: 65567 AN: 110435 Hom.: 13955 Cov.: 22 AF XY: 0.594 AC XY: 19421 AN XY: 32721

African (AFR) AF: 0.486 AC: 14780 AN: 30419

American (AMR) AF: 0.652 AC: 6869 AN: 10537

Ashkenazi Jewish (ASJ) AF: 0.577 AC: 1517 AN: 2630

East Asian (EAS) AF: 0.576 AC: 1989 AN: 3454

South Asian (SAS) AF: 0.766 AC: 2010 AN: 2623

European-Finnish (FIN) AF: 0.632 AC: 3700 AN: 5855

Middle Eastern (MID) AF: 0.634 AC: 135 AN: 213

European-Non Finnish (NFE) AF: 0.634 AC: 33316 AN: 52534

Other (OTH) AF: 0.584 AC: 879 AN: 1505

Alfa AF: 0.337 Hom.: 6887

Bravo AF: 0.590

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Adrenoleukodystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.9
DANN	Benign	0.49
PhyloP100		1.1
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: rs4898368; hg19: chrX-153008911; COSMIC: COSV54384200; COSMIC: COSV54384200;