NM_000033.4:c.1780+322A>C

Variant names:

• chrX-153741041-A-C
• rs11156606
• NM_000033.4:c.1780+322A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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 -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 VariationId 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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCD1	NM_000033.4	MANE Select	c.1780+322A>C		intron	N/A	NP_000024.2
	ABCD1	NM_001440747.1		c.2080+322A>C		intron	N/A	NP_001427676.1
	PLXNB3-AS1	NR_199693.1		n.90-2463T>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCD1	ENST00000218104.6	TSL:1 MANE Select	c.1780+322A>C		intron	N/A	ENSP00000218104.3
	PLXNB3-AS1	ENST00000434284.1	TSL:3	n.72-2463T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.262 AC: 29371 AN: 112088 Hom.: 4970 Cov.: 24

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

African (AFR) AF: 0.641 AC: 19741 AN: 30821

American (AMR) AF: 0.130 AC: 1398 AN: 10720

Ashkenazi Jewish (ASJ) AF: 0.0694 AC: 184 AN: 2650

East Asian (EAS) AF: 0.0871 AC: 308 AN: 3538

South Asian (SAS) AF: 0.155 AC: 423 AN: 2729

European-Finnish (FIN) AF: 0.110 AC: 680 AN: 6180

Middle Eastern (MID) AF: 0.0776 AC: 17 AN: 219

European-Non Finnish (NFE) AF: 0.119 AC: 6320 AN: 53072

Other (OTH) AF: 0.220 AC: 337 AN: 1532

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

Aug 06, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.5
DANN	Benign	0.35
PhyloP100		-1.3
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: rs11156606; hg19: chrX-153006495;