rs372309740

Variant names:

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.2112G>A(p.Ala704Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000209 in 1,192,550 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 89 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. A704A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., 19 hem., cov: 24)

Exomes 𝑓: 0.00018 ( 0 hom. 70 hem. )

Consequence

ABCD1
NM_000033.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -6.71

Publications

0 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-153743609-G-A is Benign according to our data. Variant chrX-153743609-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 528349.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-6.71 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000452 (51/112759) while in subpopulation AMR AF = 0.00195 (21/10790). AF 95% confidence interval is 0.0013. There are 0 homozygotes in GnomAd4. There are 19 alleles in the male GnomAd4 subpopulation. Median coverage is 24. This position passed quality control check.

BS2

High AC in GnomAd4 at 51 XL,AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCD1	NM_000033.4 link	c.2112G>A	p.Ala704Ala	synonymous_variant	Exon 10 of 10	ENST00000218104.6	NP_000024.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCD1	ENST00000218104.6 link	c.2112G>A	p.Ala704Ala	synonymous_variant	Exon 10 of 10	1	NM_000033.4	ENSP00000218104.3
PLXNB3-AS1	ENST00000434284.1 link	n.72-5031C>T		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.000453

AC:

AN:

112707

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000644

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00195

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000357

Gnomad FIN

AF:

0.000160

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000470

Gnomad OTH

AF:

0.000657

GnomAD2 exomes

AF:

0.000290

AC:

AN:

144873

AF XY:

0.000266

show subpopulations

Gnomad AFR exome

AF:

0.000110

Gnomad AMR exome

AF:

0.000292

Gnomad ASJ exome

AF:

0.000149

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000511

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000183

AC:

198

AN:

1079791

Hom.:

Cov.:

AF XY:

0.000199

AC XY:

AN XY:

351939

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25974

American (AMR)

AF:

0.000182

AC:

AN:

32903

Ashkenazi Jewish (ASJ)

AF:

0.000105

AC:

AN:

19051

East Asian (EAS)

AF:

0.00

AC:

AN:

29228

South Asian (SAS)

AF:

0.0000773

AC:

AN:

51767

European-Finnish (FIN)

AF:

0.0000259

AC:

AN:

38564

Middle Eastern (MID)

AF:

0.00383

AC:

AN:

2874

European-Non Finnish (NFE)

AF:

0.000188

AC:

157

AN:

834126

Other (OTH)

AF:

0.000375

AC:

AN:

45304

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.000452

AC:

AN:

112759

Hom.:

Cov.:

AF XY:

0.000544

AC XY:

AN XY:

34947

show subpopulations

African (AFR)

AF:

0.0000642

AC:

AN:

31135

American (AMR)

AF:

0.00195

AC:

AN:

10790

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2652

East Asian (EAS)

AF:

0.00

AC:

AN:

3539

South Asian (SAS)

AF:

0.000358

AC:

AN:

2797

European-Finnish (FIN)

AF:

0.000160

AC:

AN:

6241

Middle Eastern (MID)

AF:

0.00

AC:

AN:

219

European-Non Finnish (NFE)

AF:

0.000470

AC:

AN:

53161

Other (OTH)

AF:

0.000649

AC:

AN:

1541

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

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:

0.000304

Hom.:

Bravo

AF:

0.000378

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Adrenoleukodystrophy

Benign:1

Jan 15, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Jan 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ABCD1: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.35

(source)

DANN

Benign

0.93

PhyloP100

-6.7

Mutation Taster

=99/1

polymorphism

(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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over