chr1-94451846-T-C

Position:

• chr1-94451846-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCD3	NM_002858.4	c.111-6761T>C		intron_variant		ENST00000370214.9	NP_002849.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCD3	ENST00000370214.9	c.111-6761T>C		intron_variant		1	NM_002858.4	ENSP00000359233	P3
ABCD3	ENST00000315713.5	c.111-6761T>C		intron_variant		1		ENSP00000326880
ABCD3	ENST00000647998.2	c.111-6761T>C		intron_variant				ENSP00000497921	A1
ABCD3	ENST00000468860.1	n.188-6761T>C		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.0894

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.165

Gnomad4 SAS AF: 0.185

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.117

Alfa AF: 0.124 Hom.: 756

Bravo AF: 0.122

Asia WGS AF: 0.180 AC: 625 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.0
DANN	Benign	0.57

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

Publications

LitVar

Other links and lift over

dbSNP: rs4148057; hg19: chr1-94917402; COSMIC: COSV59865648;