rs2147794

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-94458490-A-G
• chr1-94458490-A-T

Variant summary

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

The NM_002858.4(ABCD3):​c.111-117A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 870,726 control chromosomes in the GnomAD database, including 82,668 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 0.36 (11409 hom., cov: 31)
  • Exomes 𝑓: 0.44 (71259 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.358 AC: 54461 AN: 151988 Hom.: 11409 Cov.: 31

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.656

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.478

Gnomad OTH AF: 0.432

GnomAD4 exome AF: 0.436 AC: 313072 AN: 718620 Hom.: 71259 AF XY: 0.436 AC XY: 166603 AN XY: 382134

African (AFR) AF: 0.138 AC: 2474 AN: 17882

American (AMR) AF: 0.386 AC: 13706 AN: 35478

Ashkenazi Jewish (ASJ) AF: 0.451 AC: 9184 AN: 20354

East Asian (EAS) AF: 0.222 AC: 7684 AN: 34604

South Asian (SAS) AF: 0.376 AC: 24389 AN: 64802

European-Finnish (FIN) AF: 0.365 AC: 18413 AN: 50400

Middle Eastern (MID) AF: 0.554 AC: 2014 AN: 3634

European-Non Finnish (NFE) AF: 0.482 AC: 219899 AN: 456204

Other (OTH) AF: 0.434 AC: 15309 AN: 35262

GnomAD4 genome AF: 0.358 AC: 54454 AN: 152106 Hom.: 11409 Cov.: 31 AF XY: 0.352 AC XY: 26160 AN XY: 74378

African (AFR) AF: 0.143 AC: 5940 AN: 41532

American (AMR) AF: 0.407 AC: 6220 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 1528 AN: 3468

East Asian (EAS) AF: 0.214 AC: 1107 AN: 5170

South Asian (SAS) AF: 0.351 AC: 1692 AN: 4816

European-Finnish (FIN) AF: 0.366 AC: 3861 AN: 10556

Middle Eastern (MID) AF: 0.545 AC: 159 AN: 292

European-Non Finnish (NFE) AF: 0.478 AC: 32455 AN: 67964

Other (OTH) AF: 0.425 AC: 896 AN: 2110

Alfa AF: 0.427 Hom.: 8047

Bravo AF: 0.356

Asia WGS AF: 0.256 AC: 893 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.1
DANN	Benign	0.74
PhyloP100		0.42
Mutation Taster		=99/1	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: rs2147794; hg19: chr1-94924046; COSMIC: COSV59865570;