14-74286199-A-C

Position:

• chr14-74286199-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005050.4(ABCD4):​c.*262T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 393,800 control chromosomes in the GnomAD database, including 7,417 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.18 (3212 hom., cov: 33)
  • Exomes 𝑓: 0.16 (4205 hom.)
• Consequence: ABCD4 NM_005050.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.269

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 14-74286199-A-C is Benign according to our data. Variant chr14-74286199-A-C is described in ClinVar as [Benign]. Clinvar id is 1262596.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCD4	NM_005050.4	c.*262T>G		3_prime_UTR_variant	19/19	ENST00000356924.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCD4	ENST00000356924.9	c.*262T>G		3_prime_UTR_variant	19/19	1	NM_005050.4	P1
ABCD4	ENST00000481348.5	c.*420T>G		3_prime_UTR_variant, NMD_transcript_variant	8/8	5
ABCD4	ENST00000481935.5	c.*1955T>G		3_prime_UTR_variant, NMD_transcript_variant	17/17	5

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27228 AN: 152004 Hom.: 3203 Cov.: 33

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.487

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.0761

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.193

GnomAD4 exome AF: 0.155 AC: 37518 AN: 241676 Hom.: 4205 Cov.: 0 AF XY: 0.155 AC XY: 19301 AN XY: 124742

Gnomad4 AFR exome AF: 0.290

Gnomad4 AMR exome AF: 0.147

Gnomad4 ASJ exome AF: 0.164

Gnomad4 EAS exome AF: 0.455

Gnomad4 SAS exome AF: 0.172

Gnomad4 FIN exome AF: 0.0850

Gnomad4 NFE exome AF: 0.116

Gnomad4 OTH exome AF: 0.169

GnomAD4 genome AF: 0.179 AC: 27272 AN: 152124 Hom.: 3212 Cov.: 33 AF XY: 0.179 AC XY: 13300 AN XY: 74364

Gnomad4 AFR AF: 0.291

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.487

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.0761

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.194

Alfa AF: 0.131 Hom.: 1715

Bravo AF: 0.193

Asia WGS AF: 0.311 AC: 1078 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.33
DANN	Benign	0.62

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

Other links and lift over

dbSNP: rs2466; hg19: chr14-74752902;