12-39562000-T-C

Variant names:

• chr12-39562000-T-C
• rs4284427
• NM_005164.4:c.2004-7869A>G

Variant summary

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

The NM_005164.4(ABCD2):​c.2004-7869A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 152,014 control chromosomes in the GnomAD database, including 11,044 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 0.35 (11044 hom., cov: 32)
• Consequence: ABCD2 NM_005164.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• Publications: 2 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005164.4. 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
	ABCD2	NM_005164.4	MANE Select	c.2004-7869A>G		intron	N/A	NP_005155.1	Q9UBJ2
	ABCD2	NM_001412789.1		c.1878-7869A>G		intron	N/A	NP_001399718.1
	ABCD2	NM_001412791.1		c.1707-7869A>G		intron	N/A	NP_001399720.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCD2	ENST00000308666.4	TSL:1 MANE Select	c.2004-7869A>G		intron	N/A	ENSP00000310688.3	Q9UBJ2
	ABCD2	ENST00000961978.1		c.1983-7869A>G		intron	N/A	ENSP00000632037.1
	ABCD2	ENST00000961977.1		c.1872-7869A>G		intron	N/A	ENSP00000632036.1

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52654 AN: 151894 Hom.: 11003 Cov.: 32

Gnomad AFR AF: 0.590

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.332

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

GnomAD4 genome AF: 0.347 AC: 52746 AN: 152014 Hom.: 11044 Cov.: 32 AF XY: 0.347 AC XY: 25798 AN XY: 74330

African (AFR) AF: 0.591 AC: 24486 AN: 41438

American (AMR) AF: 0.281 AC: 4288 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 838 AN: 3466

East Asian (EAS) AF: 0.422 AC: 2186 AN: 5186

South Asian (SAS) AF: 0.462 AC: 2230 AN: 4822

European-Finnish (FIN) AF: 0.182 AC: 1930 AN: 10588

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.232 AC: 15742 AN: 67928

Other (OTH) AF: 0.336 AC: 710 AN: 2112

Alfa AF: 0.285 Hom.: 11456

Bravo AF: 0.363

Asia WGS AF: 0.441 AC: 1519 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.8
DANN	Benign	0.49
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: rs4284427; hg19: chr12-39955802;