1-94492822-A-G

Variant names:

• chr1-94492822-A-G
• rs1749541
• NM_002858.4:c.1386+1575A>G

Variant summary

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

The NM_002858.4(ABCD3):​c.1386+1575A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 152,042 control chromosomes in the GnomAD database, including 41,666 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 (41666 hom., cov: 31)
• Consequence: ABCD3 NM_002858.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.29
• 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002858.4. 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
	ABCD3	NM_002858.4	MANE Select	c.1386+1575A>G		intron	N/A	NP_002849.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCD3	ENST00000370214.9	TSL:1 MANE Select	c.1386+1575A>G		intron	N/A	ENSP00000359233.4
	ABCD3	ENST00000484213.1	TSL:1	n.2236+1575A>G		intron	N/A
	ABCD3	ENST00000647998.2		c.1386+1575A>G		intron	N/A	ENSP00000497921.2

Frequencies

GnomAD3 genomes AF: 0.737 AC: 111965 AN: 151924 Hom.: 41617 Cov.: 31

Gnomad AFR AF: 0.674

Gnomad AMI AF: 0.853

Gnomad AMR AF: 0.825

Gnomad ASJ AF: 0.716

Gnomad EAS AF: 0.527

Gnomad SAS AF: 0.640

Gnomad FIN AF: 0.688

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.785

Gnomad OTH AF: 0.776

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

GnomAD4 genome AF: 0.737 AC: 112074 AN: 152042 Hom.: 41666 Cov.: 31 AF XY: 0.731 AC XY: 54360 AN XY: 74320

African (AFR) AF: 0.674 AC: 27965 AN: 41484

American (AMR) AF: 0.825 AC: 12602 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.716 AC: 2486 AN: 3472

East Asian (EAS) AF: 0.527 AC: 2728 AN: 5172

South Asian (SAS) AF: 0.643 AC: 3096 AN: 4818

European-Finnish (FIN) AF: 0.688 AC: 7257 AN: 10552

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.785 AC: 53321 AN: 67960

Other (OTH) AF: 0.771 AC: 1627 AN: 2110

Alfa AF: 0.769 Hom.: 113163

Bravo AF: 0.749

Asia WGS AF: 0.585 AC: 2037 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.099
DANN	Benign	0.47
PhyloP100		-2.3
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: rs1749541; hg19: chr1-94958378;