chrX-153737230-G-C

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_ModerateBP7BS2

The NM_000033.4(ABCD1):​c.1467G>C​(p.Val489Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000182 in 1,096,884 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. V489V) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 24)
Exomes 𝑓: 0.0000018 ( 0 hom. 2 hem. )

Consequence

ABCD1
NM_000033.4 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.04

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

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4
Computational evidence support a benign effect (REVEL=0.045).
BP7
Synonymous conserved (PhyloP=1.04 with no splicing effect.
BS2
High Hemizygotes in GnomAdExome4 at 2 XL,AD gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ABCD1NM_000033.4 linkc.1467G>C p.Val489Val synonymous_variant Exon 5 of 10 ENST00000218104.6 NP_000024.2 P33897

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ABCD1ENST00000218104.6 linkc.1467G>C p.Val489Val synonymous_variant Exon 5 of 10 1 NM_000033.4 ENSP00000218104.3 P33897
ABCD1ENST00000443684.2 linkn.470G>C non_coding_transcript_exon_variant Exon 4 of 6 3
PLXNB3-AS1ENST00000434284.1 linkn.580+840C>G intron_variant Intron 2 of 2 3

Frequencies

GnomAD3 genomes
Cov.:
24
GnomAD4 exome
AF:
0.00000182
AC:
2
AN:
1096884
Hom.:
0
Cov.:
31
AF XY:
0.00000551
AC XY:
2
AN XY:
362656
show subpopulations
African (AFR)
AF:
0.0000758
AC:
2
AN:
26398
American (AMR)
AF:
0.00
AC:
0
AN:
35185
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
19383
East Asian (EAS)
AF:
0.00
AC:
0
AN:
30187
South Asian (SAS)
AF:
0.00
AC:
0
AN:
54084
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
39561
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4136
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
841882
Other (OTH)
AF:
0.00
AC:
0
AN:
46068
GnomAD4 genome
Cov.:
24
Alfa
AF:
0.00
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.47
CADD
Benign
6.1
DANN
Benign
0.83
PhyloP100
1.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

Other links and lift over

dbSNP: rs782516659; hg19: chrX-153002684; API