1-94451846-T-C

Variant names:

• chr1-94451846-T-C
• rs4148057
• NM_002858.4:c.111-6761T>C

Variant summary

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

The NM_002858.4(ABCD3):​c.111-6761T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,170 control chromosomes in the GnomAD database, including 1,251 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 0.13 (1251 hom., cov: 32)
• Consequence: ABCD3 NM_002858.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.114
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCD3	NM_002858.4	MANE Select	c.111-6761T>C		intron	N/A	NP_002849.1
	ABCD3	NM_001122674.2		c.111-6761T>C		intron	N/A	NP_001116146.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCD3	ENST00000370214.9	TSL:1 MANE Select	c.111-6761T>C		intron	N/A	ENSP00000359233.4
	ABCD3	ENST00000315713.5	TSL:1	c.111-6761T>C		intron	N/A	ENSP00000326880.5
	ABCD3	ENST00000866889.1		c.111-3887T>C		intron	N/A	ENSP00000536948.1

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19297 AN: 152052 Hom.: 1255 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.0681

Gnomad AMR AF: 0.0897

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.115

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.127 AC: 19282 AN: 152170 Hom.: 1251 Cov.: 32 AF XY: 0.127 AC XY: 9473 AN XY: 74408

African (AFR) AF: 0.134 AC: 5550 AN: 41504

American (AMR) AF: 0.0894 AC: 1367 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 504 AN: 3470

East Asian (EAS) AF: 0.165 AC: 856 AN: 5180

South Asian (SAS) AF: 0.185 AC: 893 AN: 4826

European-Finnish (FIN) AF: 0.136 AC: 1445 AN: 10590

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8323 AN: 67990

Other (OTH) AF: 0.117 AC: 247 AN: 2110

Alfa AF: 0.123 Hom.: 2592

Bravo AF: 0.122

Asia WGS AF: 0.180 AC: 625 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.0
DANN	Benign	0.57
PhyloP100		-0.11
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: rs4148057; hg19: chr1-94917402; COSMIC: COSV59865648;