ENST00000484213.1:n.2930A>T

Variant names:

• chr1-94517229-A-T
• rs662813
• ENST00000484213.1:n.2930A>T

Variant summary

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

The ENST00000484213.1(ABCD3):​n.2930A>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 739,320 control chromosomes in the GnomAD database, including 21,934 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 0.26 (4873 hom., cov: 31)
  • Exomes 𝑓: 0.27 (17061 hom.)
• Consequence: ABCD3 ENST00000484213.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.269
• Publications: 4 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCD3	NM_002858.4	c.*100A>T		3_prime_UTR_variant	Exon 23 of 23	ENST00000370214.9	NP_002849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCD3	ENST00000484213.1	n.2930A>T		non_coding_transcript_exon_variant	Exon 14 of 14	1
ABCD3	ENST00000370214.9	c.*100A>T		3_prime_UTR_variant	Exon 23 of 23	1	NM_002858.4	ENSP00000359233.4
ABCD3	ENST00000464165.1	n.1907A>T		non_coding_transcript_exon_variant	Exon 2 of 2	2
ABCD3	ENST00000647998.2	c.*100A>T		3_prime_UTR_variant	Exon 23 of 23			ENSP00000497921.2

Frequencies

GnomAD3 genomes AF: 0.256 AC: 37631 AN: 146964 Hom.: 4878 Cov.: 31

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.260

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.219

GnomAD4 exome AF: 0.269 AC: 159253 AN: 592254 Hom.: 17061 Cov.: 9 AF XY: 0.273 AC XY: 86462 AN XY: 316976

African (AFR) AF: 0.313 AC: 4499 AN: 14392

American (AMR) AF: 0.168 AC: 4303 AN: 25666

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 4979 AN: 15884

East Asian (EAS) AF: 0.451 AC: 13574 AN: 30126

South Asian (SAS) AF: 0.349 AC: 19996 AN: 57254

European-Finnish (FIN) AF: 0.351 AC: 13385 AN: 38140

Middle Eastern (MID) AF: 0.241 AC: 649 AN: 2696

European-Non Finnish (NFE) AF: 0.237 AC: 89848 AN: 379692

Other (OTH) AF: 0.282 AC: 8020 AN: 28404

GnomAD4 genome AF: 0.256 AC: 37636 AN: 147066 Hom.: 4873 Cov.: 31 AF XY: 0.263 AC XY: 18840 AN XY: 71730

African (AFR) AF: 0.290 AC: 11615 AN: 40108

American (AMR) AF: 0.178 AC: 2611 AN: 14674

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 981 AN: 3396

East Asian (EAS) AF: 0.472 AC: 2388 AN: 5060

South Asian (SAS) AF: 0.360 AC: 1702 AN: 4734

European-Finnish (FIN) AF: 0.323 AC: 3236 AN: 10030

Middle Eastern (MID) AF: 0.262 AC: 76 AN: 290

European-Non Finnish (NFE) AF: 0.219 AC: 14442 AN: 65860

Other (OTH) AF: 0.224 AC: 451 AN: 2010

Alfa AF: 0.234 Hom.: 577

Bravo AF: 0.236

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.24
DANN	Benign	0.13
PhyloP100		-0.27
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: rs662813; hg19: chr1-94982785; COSMIC: COSV64642885;