rs681187

Variant names:

• chr1-94475820-G-A
• rs681187
• NM_002858.4:c.627+83G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-94475820-G-A
• chr1-94475820-G-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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]

ABCD3 Gene-Disease associations (from GenCC):

• congenital bile acid synthesis defect 5

  Inheritance: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ABCD3	NM_002858.4	c.627+83G>A		intron_variant	Intron 7 of 22	ENST00000370214.9	NP_002849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCD3	ENST00000370214.9	c.627+83G>A		intron_variant	Intron 7 of 22	1	NM_002858.4	ENSP00000359233.4
ABCD3	ENST00000315713.5	c.627+83G>A		intron_variant	Intron 7 of 8	1		ENSP00000326880.5
ABCD3	ENST00000647998.2	c.627+83G>A		intron_variant	Intron 7 of 22			ENSP00000497921.2
ABCD3	ENST00000468860.1	n.*126G>A		downstream_gene_variant		3

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

African (AFR) AF: 0.681 AC: 16274 AN: 23898

American (AMR) AF: 0.860 AC: 30951 AN: 35970

Ashkenazi Jewish (ASJ) AF: 0.722 AC: 16259 AN: 22516

East Asian (EAS) AF: 0.562 AC: 19186 AN: 34128

South Asian (SAS) AF: 0.660 AC: 46701 AN: 70798

European-Finnish (FIN) AF: 0.683 AC: 33200 AN: 48608

Middle Eastern (MID) AF: 0.787 AC: 2627 AN: 3338

European-Non Finnish (NFE) AF: 0.788 AC: 593123 AN: 752590

Other (OTH) AF: 0.747 AC: 33833 AN: 45312

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

African (AFR) AF: 0.677 AC: 28091 AN: 41466

American (AMR) AF: 0.826 AC: 12613 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.717 AC: 2489 AN: 3470

East Asian (EAS) AF: 0.528 AC: 2731 AN: 5176

South Asian (SAS) AF: 0.645 AC: 3106 AN: 4816

European-Finnish (FIN) AF: 0.689 AC: 7241 AN: 10504

Middle Eastern (MID) AF: 0.731 AC: 215 AN: 294

European-Non Finnish (NFE) AF: 0.785 AC: 53334 AN: 67960

Other (OTH) AF: 0.774 AC: 1638 AN: 2116

Alfa AF: 0.767 Hom.: 23883

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
PhyloP100		0.019
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: rs681187; hg19: chr1-94941376;