Variant chr14-74286438-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_005050.4(ABCD4):c.*23G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00774 in 1,613,570 control chromosomes in the GnomAD database, including 879 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.042 ( 492 hom., cov: 33)

Exomes 𝑓: 0.0042 ( 387 hom. )

Consequence

ABCD4
NM_005050.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.808

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 14-74286438-C-T is Benign according to our data. Variant chr14-74286438-C-T is described in ClinVar as [Benign]. Clinvar id is 1292530.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.143 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.*23G>A		3_prime_UTR_variant	19/19	ENST00000356924.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCD4	ENST00000356924.9 linkuse as main transcript	c.*23G>A		3_prime_UTR_variant	19/19	1	NM_005050.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0417

AC:

6348

AN:

152202

Hom.:

492

Cov.:

show subpopulations

Gnomad AFR

AF:

0.146

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0146

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.0301

GnomAD3 exomes

AF:

0.0106

AC:

2674

AN:

251210

Hom.:

188

AF XY:

0.00769

AC XY:

1045

AN XY:

135836

show subpopulations

Gnomad AFR exome

AF:

0.148

Gnomad AMR exome

AF:

0.00616

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000211

Gnomad OTH exome

AF:

0.00425

GnomAD4 exome

AF:

0.00419

AC:

6126

AN:

1461250

Hom.:

387

Cov.:

AF XY:

0.00360

AC XY:

2617

AN XY:

726990

show subpopulations

Gnomad4 AFR exome

AF:

0.150

Gnomad4 AMR exome

AF:

0.00698

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000220

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000152

Gnomad4 OTH exome

AF:

0.00931

GnomAD4 genome

AF:

0.0417

AC:

6359

AN:

152320

Hom.:

492

Cov.:

AF XY:

0.0393

AC XY:

2927

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.146

Gnomad4 AMR

AF:

0.0146

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.0298

Alfa

AF:

0.00874

Hom.:

Bravo

AF:

0.0474

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 08, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

6.3

DANN

Benign

0.76

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