1-94458490-A-T

Variant names:

• chr1-94458490-A-T
• rs2147794
• NM_002858.4:c.111-117A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002858.4(ABCD3):​c.111-117A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000556 in 720,018 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000056 (0 hom.)
• Consequence: ABCD3 NM_002858.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.418
• Publications: 6 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCD3	NM_002858.4	c.111-117A>T		intron_variant	Intron 1 of 22	ENST00000370214.9	NP_002849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCD3	ENST00000370214.9	c.111-117A>T		intron_variant	Intron 1 of 22	1	NM_002858.4	ENSP00000359233.4
ABCD3	ENST00000315713.5	c.111-117A>T		intron_variant	Intron 1 of 8	1		ENSP00000326880.5
ABCD3	ENST00000647998.2	c.111-117A>T		intron_variant	Intron 1 of 22			ENSP00000497921.2
ABCD3	ENST00000468860.1	n.188-117A>T		intron_variant	Intron 2 of 7	3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000556 AC: 4 AN: 720018 Hom.: 0 AF XY: 0.00000784 AC XY: 3 AN XY: 382842

African (AFR) AF: 0.00 AC: 0 AN: 17894

American (AMR) AF: 0.00 AC: 0 AN: 35536

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20384

East Asian (EAS) AF: 0.00 AC: 0 AN: 34642

South Asian (SAS) AF: 0.00 AC: 0 AN: 64890

European-Finnish (FIN) AF: 0.0000396 AC: 2 AN: 50474

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3640

European-Non Finnish (NFE) AF: 0.00000437 AC: 2 AN: 457244

Other (OTH) AF: 0.00 AC: 0 AN: 35314

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 8047

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.7
DANN	Benign	0.70
PhyloP100		0.42

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: rs2147794; hg19: chr1-94924046;