rs681187

Positions:

• chr1-94475820-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002858.4(ABCD3):​c.627+83G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.761 in 1,189,150 control chromosomes in the GnomAD database, including 346,278 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 0.74 (41780 hom., cov: 32)
  • Exomes 𝑓: 0.76 (304498 hom.)
• Consequence: ABCD3 NM_002858.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0190

Genes affected

ABCD3 (HGNC:67): (ATP binding cassette subfamily D member 3) 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 likely plays an important role in peroxisome biogenesis. Mutations have been associated with some forms of Zellweger syndrome, a heterogeneous group of peroxisome assembly disorders. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.814 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCD3	NM_002858.4	c.627+83G>A		intron_variant		ENST00000370214.9	NP_002849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCD3	ENST00000370214.9	c.627+83G>A		intron_variant		1	NM_002858.4	ENSP00000359233	P3
ABCD3	ENST00000315713.5	c.627+83G>A		intron_variant		1		ENSP00000326880
ABCD3	ENST00000647998.2	c.627+83G>A		intron_variant				ENSP00000497921	A1

Frequencies

GnomAD3 genomes AF: 0.738 AC: 112122 AN: 151874 Hom.: 41728 Cov.: 32

Gnomad AFR AF: 0.677

Gnomad AMI AF: 0.853

Gnomad AMR AF: 0.825

Gnomad ASJ AF: 0.717

Gnomad EAS AF: 0.528

Gnomad SAS AF: 0.643

Gnomad FIN AF: 0.689

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.785

Gnomad OTH AF: 0.779

GnomAD4 exome AF: 0.764 AC: 792154 AN: 1037158 Hom.: 304498 AF XY: 0.761 AC XY: 402196 AN XY: 528500

Gnomad4 AFR exome AF: 0.681

Gnomad4 AMR exome AF: 0.860

Gnomad4 ASJ exome AF: 0.722

Gnomad4 EAS exome AF: 0.562

Gnomad4 SAS exome AF: 0.660

Gnomad4 FIN exome AF: 0.683

Gnomad4 NFE exome AF: 0.788

Gnomad4 OTH exome AF: 0.747

GnomAD4 genome AF: 0.738 AC: 112236 AN: 151992 Hom.: 41780 Cov.: 32 AF XY: 0.733 AC XY: 54443 AN XY: 74304

Gnomad4 AFR AF: 0.677

Gnomad4 AMR AF: 0.826

Gnomad4 ASJ AF: 0.717

Gnomad4 EAS AF: 0.528

Gnomad4 SAS AF: 0.645

Gnomad4 FIN AF: 0.689

Gnomad4 NFE AF: 0.785

Gnomad4 OTH AF: 0.774

Alfa AF: 0.767 Hom.: 21393

Bravo AF: 0.750

Asia WGS AF: 0.575 AC: 1990 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.99
DANN	Benign	0.36

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

Publications

LitVar

Other links and lift over

dbSNP: rs681187; hg19: chr1-94941376;