rs11172502

Variant names:

• chr12-39538649-A-T
• rs11172502
• XM_017018992.3:c.2004-6589T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_017018992.3(ABCD2):​c.2004-6589T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.068 in 152,074 control chromosomes in the GnomAD database, including 538 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.068 (538 hom., cov: 32)
• Consequence: ABCD2 XM_017018992.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.526
• Publications: 3 publications found

Genes affected

ABCD2 (HGNC:66): (ATP binding cassette subfamily D member 2) 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. The function of this peroxisomal membrane protein is unknown; however this protein is speculated to function as a dimerization partner of ABCD1 and/or other peroxisomal ABC transporters. Mutations in this gene have been observed in patients with adrenoleukodystrophy, a severe demyelinating disease. This gene has been identified as a candidate for a modifier gene, accounting for the extreme variation among adrenoleukodystrophy phenotypes. This gene is also a candidate for a complement group of Zellweger syndrome, a genetically heterogeneous disorder of peroxisomal biogenesis. [provided by RefSeq, Jul 2008]

ENSG00000304421 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000803244.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000304421	ENST00000803244.1		n.-112A>T		upstream_gene	N/A
	ENSG00000304421	ENST00000803245.1		n.-117A>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.0680 AC: 10332 AN: 151956 Hom.: 535 Cov.: 32

Gnomad AFR AF: 0.0145

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.0928

Gnomad ASJ AF: 0.0464

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.0556

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0691

Gnomad OTH AF: 0.0666

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0680 AC: 10335 AN: 152074 Hom.: 538 Cov.: 32 AF XY: 0.0725 AC XY: 5391 AN XY: 74346

African (AFR) AF: 0.0144 AC: 598 AN: 41502

American (AMR) AF: 0.0929 AC: 1419 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0464 AC: 161 AN: 3472

East Asian (EAS) AF: 0.239 AC: 1234 AN: 5160

South Asian (SAS) AF: 0.281 AC: 1353 AN: 4810

European-Finnish (FIN) AF: 0.0556 AC: 588 AN: 10580

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0691 AC: 4698 AN: 67958

Other (OTH) AF: 0.0687 AC: 145 AN: 2110

Alfa AF: 0.0649 Hom.: 60

Bravo AF: 0.0663

Asia WGS AF: 0.220 AC: 764 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.8
DANN	Benign	0.74
PhyloP100		-0.53

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11172502; hg19: chr12-39932451;