14-74292356-G-C
Variant names:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_005050.4(ABCD4):āc.1049C>Gā(p.Thr350Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0241 in 1,614,040 control chromosomes in the GnomAD database, including 555 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.019 ( 37 hom., cov: 33)
Exomes š: 0.025 ( 518 hom. )
Consequence
ABCD4
NM_005050.4 missense
NM_005050.4 missense
Scores
1
5
12
Clinical Significance
Conservation
PhyloP100: 3.61
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]
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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 (MetaRNN=0.006796807).
BP6
Variant 14-74292356-G-C is Benign according to our data. Variant chr14-74292356-G-C is described in ClinVar as [Benign]. Clinvar id is 380512.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0187 (2847/152310) while in subpopulation NFE AF= 0.0272 (1853/68046). AF 95% confidence interval is 0.0262. There are 37 homozygotes in gnomad4. There are 1358 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 37 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ABCD4 | NM_005050.4 | c.1049C>G | p.Thr350Arg | missense_variant | Exon 11 of 19 | ENST00000356924.9 | NP_005041.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0187 AC: 2848AN: 152192Hom.: 37 Cov.: 33
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GnomAD3 exomes AF: 0.0180 AC: 4514AN: 251224Hom.: 60 AF XY: 0.0175 AC XY: 2378AN XY: 135778
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GnomAD4 exome AF: 0.0247 AC: 36069AN: 1461730Hom.: 518 Cov.: 34 AF XY: 0.0239 AC XY: 17394AN XY: 727158
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GnomAD4 genome AF: 0.0187 AC: 2847AN: 152310Hom.: 37 Cov.: 33 AF XY: 0.0182 AC XY: 1358AN XY: 74462
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Methylmalonic acidemia with homocystinuria, type cblJ Benign:2
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Oct 29, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 30, 2025 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 21, 2016 | 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. - |
not provided Benign:1
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
D
MetaRNN
Benign
T
MetaSVM
Uncertain
D
MutationAssessor
Benign
M
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at