rs3742801

Positions:

chr14-74292303-C-T

Variant summary

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

The NM_005050.4(ABCD4):c.1102G>A(p.Glu368Lys) 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 1,613,546 control chromosomes in the GnomAD database, including 101,224 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 7716 hom., cov: 32)

Exomes 𝑓: 0.35 ( 93508 hom. )

Consequence

ABCD4
NM_005050.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.0780

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:

ABCD4 (HGNC:):

ABCD4 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=0.0028183162).

BP6

Variant 14-74292303-C-T is Benign according to our data. Variant chr14-74292303-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 259619.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-74292303-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/exons	MANE	Protein	UniProt
ABCD4	NM_005050.4 linkuse as main transcript	c.1102G>A	p.Glu368Lys	missense_variant	11/19	ENST00000356924.9	NP_005041.1	O14678A0A024R6B9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCD4	ENST00000356924.9 linkuse as main transcript	c.1102G>A	p.Glu368Lys	missense_variant	11/19	1	NM_005050.4	ENSP00000349396.4		O14678

Frequencies

GnomAD3 genomes

AF:

0.309

AC:

46891

AN:

151916

Hom.:

7725

Cov.:

show subpopulations

Gnomad AFR

AF:

0.191

Gnomad AMI

AF:

0.467

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:

0.363

GnomAD3 exomes

AF:

0.327

AC:

82082

AN:

251102

Hom.:

14515

AF XY:

0.340

AC XY:

46137

AN XY:

135746

show subpopulations

Gnomad AFR exome

AF:

0.186

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:

0.310

Gnomad NFE exome

AF:

0.372

Gnomad OTH exome

AF:

0.372

GnomAD4 exome

AF:

0.353

AC:

515495

AN:

1461512

Hom.:

93508

Cov.:

AF XY:

0.356

AC XY:

258752

AN XY:

727074

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:

0.308

AC:

46888

AN:

152034

Hom.:

7716

Cov.:

AF XY:

0.306

AC XY:

22751

AN XY:

74306

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:

0.359

Gnomad4 FIN

AF:

0.311

Gnomad4 NFE

AF:

0.370

Gnomad4 OTH

AF:

0.364

Alfa

AF:

0.367

Hom.:

27530

Bravo

AF:

0.300

TwinsUK

AF:

0.366

AC:

1356

ALSPAC

AF:

0.354

AC:

1365

ESP6500AA

AF:

0.197

AC:

868

ESP6500EA

AF:

0.364

AC:

3128

ExAC

AF:

0.327

AC:

39739

Asia WGS

AF:

0.311

AC:

1078

AN:

3478

EpiCase

AF:

0.396

EpiControl

AF:

0.404

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 02, 2015	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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Dec 03, 2021	- -

Methylmalonic acidemia with homocystinuria, type cblJ

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.13

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.052

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.066

LIST_S2

Benign

0.85

MetaRNN

Benign

0.0028

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.66

REVEL

Uncertain

0.32

Sift

Benign

0.23

Sift4G

Benign

0.52

Polyphen

0.0020

Vest4

0.042

MPC

0.27

ClinPred

0.0080

GERP RS

1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.043

gMVP

0.74

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