X-153736097-T-C

Variant names:

• chrX-153736097-T-C
• rs200250434
• NM_000033.4:c.1082-15T>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_000033.4(ABCD1):​c.1082-15T>C 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000096 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.000016 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: ABCD1 NM_000033.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.94

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)

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant X-153736097-T-C is Benign according to our data. Variant chrX-153736097-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2855301.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCD1	NM_000033.4	c.1082-15T>C		intron_variant	Intron 2 of 9	ENST00000218104.6	NP_000024.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCD1	ENST00000218104.6	c.1082-15T>C		intron_variant	Intron 2 of 9	1	NM_000033.4	ENSP00000218104.3
PLXNB3-AS1	ENST00000434284.1	n.581-138A>G		intron_variant	Intron 2 of 2	3
ABCD1	ENST00000443684.2	n.85-15T>C		intron_variant	Intron 1 of 5	3

Frequencies

GnomAD3 genomes AF: 0.00000965 AC: 1 AN: 103678 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000362

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000112 AC: 2 AN: 179179 AF XY: 0.0000151

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000145

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000159 AC: 10 AN: 628429 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 198903

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000639 AC: 1 AN: 15658

American (AMR) AF: 0.0000332 AC: 1 AN: 30158

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11959

East Asian (EAS) AF: 0.0000694 AC: 1 AN: 14401

South Asian (SAS) AF: 0.00 AC: 0 AN: 46503

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2662

European-Non Finnish (NFE) AF: 0.0000154 AC: 7 AN: 455227

Other (OTH) AF: 0.00 AC: 0 AN: 25269

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000964 AC: 1 AN: 103734 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 30592

African (AFR) AF: 0.00 AC: 0 AN: 29050

American (AMR) AF: 0.00 AC: 0 AN: 9955

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2498

East Asian (EAS) AF: 0.000362 AC: 1 AN: 2760

South Asian (SAS) AF: 0.00 AC: 0 AN: 2010

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4784

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 208

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 50390

Other (OTH) AF: 0.00 AC: 0 AN: 1442

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Adrenoleukodystrophy Benign:1

May 01, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.5
DANN	Benign	0.45
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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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Other links and lift over

dbSNP: rs200250434; hg19: chrX-153001551;