Variant 14-74286660-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005050.4(ABCD4):c.1752+41C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0147 in 1,613,404 control chromosomes in the GnomAD database, including 613 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 84 hom., cov: 32)

Exomes 𝑓: 0.014 ( 529 hom. )

Consequence

ABCD4
NM_005050.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0270

Variant links:

Genes affected

ABCD4 (HGNC:68): (ATP binding cassette subfamily D member 4) 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. The function of this peroxisomal membrane protein is unknown. However, it is speculated that it may function as a heterodimer for another peroxisomal ABC transporter and, therefore, may modify the adrenoleukodystrophy phenotype. It may also play a role in the process of peroxisome biogenesis. Alternative splicing results in several protein-coding and non-protein-coding variants. [provided by RefSeq, Jul 2017]

ABCD4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 14-74286660-G-A is Benign according to our data. Variant chr14-74286660-G-A is described in ClinVar as [Benign]. Clinvar id is 1232910.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0844 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCD4	NM_005050.4 linkuse as main transcript	c.1752+41C>T		intron_variant		ENST00000356924.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCD4	ENST00000356924.9 linkuse as main transcript	c.1752+41C>T		intron_variant		1	NM_005050.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0189

AC:

2871

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0106

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0883

Gnomad ASJ

AF:

0.0193

Gnomad EAS

AF:

0.0289

Gnomad SAS

AF:

0.0323

Gnomad FIN

AF:

0.00518

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00897

Gnomad OTH

AF:

0.0210

GnomAD3 exomes

AF:

0.0303

AC:

7570

AN:

250122

Hom.:

387

AF XY:

0.0261

AC XY:

3531

AN XY:

135260

show subpopulations

Gnomad AFR exome

AF:

0.00981

Gnomad AMR exome

AF:

0.130

Gnomad ASJ exome

AF:

0.0177

Gnomad EAS exome

AF:

0.0288

Gnomad SAS exome

AF:

0.0270

Gnomad FIN exome

AF:

0.00671

Gnomad NFE exome

AF:

0.00981

Gnomad OTH exome

AF:

0.0221

GnomAD4 exome

AF:

0.0142

AC:

20786

AN:

1461074

Hom.:

529

Cov.:

AF XY:

0.0139

AC XY:

10122

AN XY:

726730

show subpopulations

Gnomad4 AFR exome

AF:

0.00852

Gnomad4 AMR exome

AF:

0.124

Gnomad4 ASJ exome

AF:

0.0200

Gnomad4 EAS exome

AF:

0.0244

Gnomad4 SAS exome

AF:

0.0249

Gnomad4 FIN exome

AF:

0.00633

Gnomad4 NFE exome

AF:

0.00894

Gnomad4 OTH exome

AF:

0.0154

GnomAD4 genome

AF:

0.0189

AC:

2883

AN:

152330

Hom.:

Cov.:

AF XY:

0.0207

AC XY:

1545

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0107

Gnomad4 AMR

AF:

0.0883

Gnomad4 ASJ

AF:

0.0193

Gnomad4 EAS

AF:

0.0289

Gnomad4 SAS

AF:

0.0328

Gnomad4 FIN

AF:

0.00518

Gnomad4 NFE

AF:

0.00897

Gnomad4 OTH

AF:

0.0208

Alfa

AF:

0.0129

Hom.:

Bravo

AF:

0.0252

Asia WGS

AF:

0.0370

AC:

127

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

DANN

Benign

0.76

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over