X-153743457-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_000033.4(ABCD1):​c.1992-32C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 13955 hom., 19421 hem., cov: 22)
Exomes 𝑓: 0.64 ( 147059 hom. 227195 hem. )
Failed GnomAD Quality Control

Consequence

ABCD1
NM_000033.4 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.08
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
Variant X-153743457-C-T is Benign according to our data. Variant chrX-153743457-C-T is described in ClinVar as [Benign]. Clinvar id is 439347.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ABCD1NM_000033.4 linkuse as main transcriptc.1992-32C>T intron_variant ENST00000218104.6 NP_000024.2 P33897
ABCD1XM_047441916.1 linkuse as main transcriptc.2292-32C>T intron_variant XP_047297872.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ABCD1ENST00000218104.6 linkuse as main transcriptc.1992-32C>T intron_variant 1 NM_000033.4 ENSP00000218104.3 P33897
PLXNB3-AS1ENST00000434284.1 linkuse as main transcriptn.72-4879G>A intron_variant 3

Frequencies

GnomAD3 genomes
AF:
0.594
AC:
65532
AN:
110381
Hom.:
13954
Cov.:
22
AF XY:
0.593
AC XY:
19381
AN XY:
32657
show subpopulations
Gnomad AFR
AF:
0.486
Gnomad AMI
AF:
0.559
Gnomad AMR
AF:
0.651
Gnomad ASJ
AF:
0.577
Gnomad EAS
AF:
0.576
Gnomad SAS
AF:
0.765
Gnomad FIN
AF:
0.632
Gnomad MID
AF:
0.637
Gnomad NFE
AF:
0.634
Gnomad OTH
AF:
0.581
GnomAD3 exomes
AF:
0.628
AC:
97817
AN:
155788
Hom.:
21314
AF XY:
0.629
AC XY:
30750
AN XY:
48858
show subpopulations
Gnomad AFR exome
AF:
0.476
Gnomad AMR exome
AF:
0.670
Gnomad ASJ exome
AF:
0.588
Gnomad EAS exome
AF:
0.535
Gnomad SAS exome
AF:
0.766
Gnomad FIN exome
AF:
0.646
Gnomad NFE exome
AF:
0.620
Gnomad OTH exome
AF:
0.639
GnomAD4 exome
Data not reliable, filtered out with message: InbreedingCoeff
AF:
0.636
AC:
689259
AN:
1083863
Hom.:
147059
Cov.:
41
AF XY:
0.642
AC XY:
227195
AN XY:
354053
show subpopulations
Gnomad4 AFR exome
AF:
0.484
Gnomad4 AMR exome
AF:
0.673
Gnomad4 ASJ exome
AF:
0.589
Gnomad4 EAS exome
AF:
0.601
Gnomad4 SAS exome
AF:
0.763
Gnomad4 FIN exome
AF:
0.650
Gnomad4 NFE exome
AF:
0.633
Gnomad4 OTH exome
AF:
0.633
GnomAD4 genome
Data not reliable, filtered out with message: InbreedingCoeff
AF:
0.594
AC:
65567
AN:
110435
Hom.:
13955
Cov.:
22
AF XY:
0.594
AC XY:
19421
AN XY:
32721
show subpopulations
Gnomad4 AFR
AF:
0.486
Gnomad4 AMR
AF:
0.652
Gnomad4 ASJ
AF:
0.577
Gnomad4 EAS
AF:
0.576
Gnomad4 SAS
AF:
0.766
Gnomad4 FIN
AF:
0.632
Gnomad4 NFE
AF:
0.634
Gnomad4 OTH
AF:
0.584
Alfa
AF:
0.337
Hom.:
6887
Bravo
AF:
0.590

ClinVar

Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingARUP Laboratories, Molecular Genetics and Genomics, ARUP LaboratoriesApr 02, 2020- -
Benign, criteria provided, single submitterclinical testingGeneDxAug 06, 2019- -
Adrenoleukodystrophy Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 14, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
CADD
Benign
1.9
DANN
Benign
0.49

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs4898368; hg19: chrX-153008911; COSMIC: COSV54384200; COSMIC: COSV54384200; API