1-94475820-G-C

Variant names:

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

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.627+83G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000674 in 1,038,912 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: 32)
  • Exomes 𝑓: 0.0000067 (0 hom.)
• Consequence: ABCD3 NM_002858.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0190
• Publications: 0 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=-0.92).

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.627+83G>C		intron	N/A	NP_002849.1
	ABCD3	NM_001122674.2		c.627+83G>C		intron	N/A	NP_001116146.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCD3	ENST00000370214.9	TSL:1 MANE Select	c.627+83G>C		intron	N/A	ENSP00000359233.4
	ABCD3	ENST00000315713.5	TSL:1	c.627+83G>C		intron	N/A	ENSP00000326880.5
	ABCD3	ENST00000647998.2		c.627+83G>C		intron	N/A	ENSP00000497921.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000674 AC: 7 AN: 1038912 Hom.: 0 AF XY: 0.00000756 AC XY: 4 AN XY: 529414

African (AFR) AF: 0.00 AC: 0 AN: 23948

American (AMR) AF: 0.00 AC: 0 AN: 36008

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22534

East Asian (EAS) AF: 0.00 AC: 0 AN: 34160

South Asian (SAS) AF: 0.00 AC: 0 AN: 70904

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48658

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3344

European-Non Finnish (NFE) AF: 0.00000928 AC: 7 AN: 753982

Other (OTH) AF: 0.00 AC: 0 AN: 45374

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.83
DANN	Benign	0.57
PhyloP100		0.019

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;