dbSNP rs337592: ABCD3:n.2955A>G (chr1-94517254-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000484213.1(ABCD3):n.2955A>G 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 0.0763 in 724,756 control chromosomes in the GnomAD database, including 2,689 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 0.088 ( 693 hom., cov: 32)

Exomes 𝑓: 0.073 ( 1996 hom. )

Consequence

ABCD3
ENST00000484213.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.807

Publications

5 publications found

Variant links:

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

ABCD3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCD3	NM_002858.4 link	c.*125A>G		3_prime_UTR_variant	Exon 23 of 23	ENST00000370214.9	NP_002849.1	P28288-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ABCD3	ENST00000484213.1 link	n.2955A>G	non_coding_transcript_exon_variant	Exon 14 of 14	1
ABCD3	ENST00000370214.9 link	c.*125A>G	3_prime_UTR_variant	Exon 23 of 23	1	NM_002858.4	ENSP00000359233.4	P28288-1
ABCD3	ENST00000464165.1 link	n.1932A>G	non_coding_transcript_exon_variant	Exon 2 of 2	2
ABCD3	ENST00000647998.2 link	c.*125A>G	3_prime_UTR_variant	Exon 23 of 23			ENSP00000497921.2	A0A3B3ITW3

Frequencies

GnomAD3 genomes

AF:

0.0885

AC:

13427

AN:

151692

Hom.:

693

Cov.:

show subpopulations

Gnomad AFR

AF:

0.136

Gnomad AMI

AF:

0.0648

Gnomad AMR

AF:

0.0485

Gnomad ASJ

AF:

0.0682

Gnomad EAS

AF:

0.126

Gnomad SAS

AF:

0.124

Gnomad FIN

AF:

0.137

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0578

Gnomad OTH

AF:

0.0652

GnomAD4 exome

AF:

0.0731

AC:

41901

AN:

572946

Hom.:

1996

Cov.:

AF XY:

0.0748

AC XY:

23283

AN XY:

311228

show subpopulations

African (AFR)

AF:

0.137

AC:

1998

AN:

14588

American (AMR)

AF:

0.0313

AC:

962

AN:

30784

Ashkenazi Jewish (ASJ)

AF:

0.0583

AC:

1060

AN:

18172

East Asian (EAS)

AF:

0.116

AC:

3777

AN:

32688

South Asian (SAS)

AF:

0.118

AC:

7098

AN:

60382

European-Finnish (FIN)

AF:

0.136

AC:

5416

AN:

39958

Middle Eastern (MID)

AF:

0.0473

AC:

117

AN:

2472

European-Non Finnish (NFE)

AF:

0.0556

AC:

19146

AN:

344056

Other (OTH)

AF:

0.0780

AC:

2327

AN:

29846

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1940

3880

5820

7760

9700

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

268

536

804

1072

1340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0885

AC:

13433

AN:

151810

Hom.:

693

Cov.:

AF XY:

0.0918

AC XY:

6815

AN XY:

74214

show subpopulations

African (AFR)

AF:

0.135

AC:

5620

AN:

41478

American (AMR)

AF:

0.0484

AC:

737

AN:

15226

Ashkenazi Jewish (ASJ)

AF:

0.0682

AC:

236

AN:

3462

East Asian (EAS)

AF:

0.126

AC:

652

AN:

5168

South Asian (SAS)

AF:

0.123

AC:

593

AN:

4818

European-Finnish (FIN)

AF:

0.137

AC:

1450

AN:

10568

Middle Eastern (MID)

AF:

0.0884

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0578

AC:

3917

AN:

67778

Other (OTH)

AF:

0.0678

AC:

143

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

623

1247

1870

2494

3117

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

162

324

486

648

810

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0730

Hom.:

271

Bravo

AF:

0.0816

Asia WGS

AF:

0.145

AC:

500

AN:

3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

7.8

(source)

DANN

Benign

0.80

PhyloP100

0.81

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over