Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_000033.4(ABCD1):c.2190G>A(p.Pro730Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00124 in 1,170,183 control chromosomes in the GnomAD database, including 2 homozygotes. There are 468 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P730P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00093 ( 1 hom., 28 hem., cov: 23)

Exomes 𝑓: 0.0013 ( 1 hom. 440 hem. )

Consequence

ABCD1
NM_000033.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.00100

Publications

1 publications found

Variant links:

Genes affected

ABCD1 (HGNC:61): (ATP binding cassette subfamily D member 1) 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 is likely involved in the peroxisomal transport or catabolism of very long chain fatty acids. Defects in this gene have been identified as the underlying cause of adrenoleukodystrophy, an X-chromosome recessively inherited demyelinating disorder of the nervous system. [provided by RefSeq, Jul 2008]

ABCD1 links:

PLXNB3-AS1 (HGNC:40454): (PLXNB3 antisense RNA 1)

PLXNB3-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant X-153743687-G-A is Benign according to our data. Variant chrX-153743687-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 35640.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.001 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000929 (104/111904) while in subpopulation SAS AF = 0.00332 (9/2708). AF 95% confidence interval is 0.00173. There are 1 homozygotes in GnomAd4. There are 28 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.

BS2

High AC in GnomAd4 at 104 XL,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000033.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ABCD1	NM_000033.4	MANE Select	c.2190G>A	p.Pro730Pro	synonymous	Exon 10 of 10	NP_000024.2
ABCD1	NM_001440747.1		c.2490G>A	p.Pro830Pro	synonymous	Exon 11 of 11	NP_001427676.1
PLXNB3-AS1	NR_199693.1		n.90-5109C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABCD1	ENST00000218104.6	TSL:1 MANE Select	c.2190G>A	p.Pro730Pro	synonymous	Exon 10 of 10	ENSP00000218104.3
	PLXNB3-AS1	ENST00000434284.1	TSL:3	n.72-5109C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000939

AC:

105

AN:

111851

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000259

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000285

Gnomad SAS

AF:

0.00331

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00161

Gnomad OTH

AF:

0.00132

GnomAD2 exomes

AF:

0.000805

AC:

AN:

114276

AF XY:

0.00105

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000146

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00137

Gnomad OTH exome

AF:

0.00184

GnomAD4 exome

AF:

0.00128

AC:

1350

AN:

1058279

Hom.:

Cov.:

AF XY:

0.00128

AC XY:

440

AN XY:

343735

show subpopulations

African (AFR)

AF:

0.000119

AC:

AN:

25242

American (AMR)

AF:

0.000102

AC:

AN:

29455

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18653

East Asian (EAS)

AF:

0.00

AC:

AN:

27731

South Asian (SAS)

AF:

0.00167

AC:

AN:

50160

European-Finnish (FIN)

AF:

0.000112

AC:

AN:

35642

Middle Eastern (MID)

AF:

0.00314

AC:

AN:

2867

European-Non Finnish (NFE)

AF:

0.00147

AC:

1210

AN:

824002

Other (OTH)

AF:

0.000831

AC:

AN:

44527

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

103

155

206

258

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

192

240

<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:

0.000929

AC:

104

AN:

111904

Hom.:

Cov.:

AF XY:

0.000820

AC XY:

AN XY:

34132

show subpopulations

African (AFR)

AF:

0.000227

AC:

AN:

30904

American (AMR)

AF:

0.00

AC:

AN:

10662

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2644

East Asian (EAS)

AF:

0.000286

AC:

AN:

3502

South Asian (SAS)

AF:

0.00332

AC:

AN:

2708

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6121

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.00161

AC:

AN:

52934

Other (OTH)

AF:

0.00131

AC:

AN:

1529

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.000945

Hom.:

Bravo

AF:

0.000620

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Adrenoleukodystrophy (3)

Inborn genetic diseases (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.76

(source)

DANN

Benign

0.60

PhyloP100

-0.0010

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

NM_000033.4:c.2190G>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over