Variant X-153736104-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_000033.4(ABCD1):c.1082-8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000219 in 912,161 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 0.0000022 ( 0 hom. 0 hem. )

Consequence

ABCD1
NM_000033.4 splice_region, intron

Scores

Splicing: ADA: 0.0003252

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.586

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:

LOC124905226 (HGNC:):

LOC124905226 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant X-153736104-C-T is Benign according to our data. Variant chrX-153736104-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1931447.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
ABCD1	NM_000033.4 linkuse as main transcript	c.1082-8C>T	splice_region_variant, intron_variant		ENST00000218104.6	NP_000024.2	P33897
ABCD1	XM_047441916.1 linkuse as main transcript	c.1082-8C>T	splice_region_variant, intron_variant			XP_047297872.1
ABCD1	XM_047441917.1 linkuse as main transcript	c.1082-8C>T	splice_region_variant, intron_variant			XP_047297873.1
LOC124905226	XR_007068350.1 linkuse as main transcript	n.4247G>A	non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
ABCD1	ENST00000218104.6 linkuse as main transcript	c.1082-8C>T	splice_region_variant, intron_variant	1	NM_000033.4	ENSP00000218104.3	P33897
PLXNB3-AS1	ENST00000434284.1 linkuse as main transcript	n.581-145G>A	intron_variant	3
ABCD1	ENST00000443684.2 linkuse as main transcript	n.85-8C>T	splice_region_variant, intron_variant	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000219

AC:

AN:

912161

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

287669

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000623

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Adrenoleukodystrophy

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 17, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

3.1

DANN

Benign

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00033

dbscSNV1_RF

Benign

0.036

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over