rs4148077

Variant names:

Variant summary

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

The NM_005050.4(ABCD4):c.910G>A(p.Ala304Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 1,613,482 control chromosomes in the GnomAD database, including 101,222 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 7727 hom., cov: 32)

Exomes 𝑓: 0.35 ( 93495 hom. )

Consequence

ABCD4
NM_005050.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.657

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:

ENSG00000258559 (HGNC:):

ENSG00000258559 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.3361397E-4).

BP6

Variant 14-74292774-C-T is Benign according to our data. Variant chr14-74292774-C-T is described in ClinVar as [Benign]. Clinvar id is 259621.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-74292774-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCD4	NM_005050.4 link	c.910G>A	p.Ala304Thr	missense_variant	Exon 9 of 19	ENST00000356924.9	NP_005041.1	O14678A0A024R6B9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCD4	ENST00000356924.9 link	c.910G>A	p.Ala304Thr	missense_variant	Exon 9 of 19	1	NM_005050.4	ENSP00000349396.4		O14678

Frequencies

GnomAD3 genomes

AF:

0.309

AC:

46920

AN:

151914

Hom.:

7737

Cov.:

show subpopulations

Gnomad AFR

AF:

0.191

Gnomad AMI

AF:

0.468

Gnomad AMR

AF:

0.306

Gnomad ASJ

AF:

0.442

Gnomad EAS

AF:

0.251

Gnomad SAS

AF:

0.361

Gnomad FIN

AF:

0.311

Gnomad MID

AF:

0.560

Gnomad NFE

AF:

0.370

Gnomad OTH

AF:

0.362

GnomAD3 exomes

AF:

0.327

AC:

81980

AN:

250620

Hom.:

14440

AF XY:

0.340

AC XY:

46058

AN XY:

135420

show subpopulations

Gnomad AFR exome

AF:

0.187

Gnomad AMR exome

AF:

0.224

Gnomad ASJ exome

AF:

0.437

Gnomad EAS exome

AF:

0.242

Gnomad SAS exome

AF:

0.367

Gnomad FIN exome

AF:

0.311

Gnomad NFE exome

AF:

0.372

Gnomad OTH exome

AF:

0.374

GnomAD4 exome

AF:

0.353

AC:

515615

AN:

1461452

Hom.:

93495

Cov.:

AF XY:

0.356

AC XY:

258789

AN XY:

726972

show subpopulations

Gnomad4 AFR exome

AF:

0.185

Gnomad4 AMR exome

AF:

0.231

Gnomad4 ASJ exome

AF:

0.444

Gnomad4 EAS exome

AF:

0.242

Gnomad4 SAS exome

AF:

0.371

Gnomad4 FIN exome

AF:

0.314

Gnomad4 NFE exome

AF:

0.364

Gnomad4 OTH exome

AF:

0.360

GnomAD4 genome

AF:

0.309

AC:

46915

AN:

152030

Hom.:

7727

Cov.:

AF XY:

0.306

AC XY:

22763

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.191

Gnomad4 AMR

AF:

0.305

Gnomad4 ASJ

AF:

0.442

Gnomad4 EAS

AF:

0.251

Gnomad4 SAS

AF:

0.360

Gnomad4 FIN

AF:

0.311

Gnomad4 NFE

AF:

0.370

Gnomad4 OTH

AF:

0.362

Alfa

AF:

0.353

Hom.:

13363

Bravo

AF:

0.300

TwinsUK

AF:

0.366

AC:

1357

ALSPAC

AF:

0.355

AC:

1367

ESP6500AA

AF:

0.197

AC:

870

ESP6500EA

AF:

0.364

AC:

3129

ExAC

AF:

0.327

AC:

39709

Asia WGS

AF:

0.311

AC:

1079

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 02, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Methylmalonic acidemia with homocystinuria, type cblJ

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.16

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.040

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.85

MetaRNN

Benign

0.00073

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.30

REVEL

Uncertain

0.34

Sift

Benign

0.86

Sift4G

Benign

0.74

Polyphen

0.0030

Vest4

0.024

MPC

0.24

ClinPred

0.0050

GERP RS

2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.028

gMVP

0.58

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.

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