chr12-39538649-A-T

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCD2	XM_017018992.3	c.2004-6589T>A		intron_variant	Intron 9 of 9		XP_016874481.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000304421	ENST00000803244.1	n.-112A>T		upstream_gene_variant
ENSG00000304421	ENST00000803245.1	n.-117A>T		upstream_gene_variant

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 v4.3

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;