1-94492822-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCD3	NM_002858.4	c.1386+1575A>G		intron_variant		ENST00000370214.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCD3	ENST00000370214.9	c.1386+1575A>G		intron_variant		1	NM_002858.4	P3
ABCD3	ENST00000484213.1	n.2236+1575A>G		intron_variant, non_coding_transcript_variant		1
ABCD3	ENST00000647998.2	c.1386+1575A>G		intron_variant				A1

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

Gnomad4 AFR AF: 0.674

Gnomad4 AMR AF: 0.825

Gnomad4 ASJ AF: 0.716

Gnomad4 EAS AF: 0.527

Gnomad4 SAS AF: 0.643

Gnomad4 FIN AF: 0.688

Gnomad4 NFE AF: 0.785

Gnomad4 OTH AF: 0.771

Alfa AF: 0.774 Hom.: 76297

Bravo AF: 0.749

Asia WGS AF: 0.585 AC: 2037 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.099
Dann	Benign	0.47

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: rs1749541; hg19: chr1-94958378;