ENST00000557177.1:c.-202C>T

Variant names:

• chr14-74303138-C-T
• rs17782508
• ENST00000557177.1:c.-202C>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000557177.1(VRTN):​c.-202C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 439,878 control chromosomes in the GnomAD database, including 24,968 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (7257 hom., cov: 33)
  • Exomes 𝑓: 0.34 (17711 hom.)
• Consequence: VRTN ENST00000557177.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.26

Genes affected

VRTN (HGNC:20223): (vertebrae development associated) Predicted to enable sequence-specific DNA binding activity and transposase activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in chromatin. [provided by Alliance of Genome Resources, Apr 2022]

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 14-74303138-C-T is Benign according to our data. Variant chr14-74303138-C-T is described in ClinVar as [Benign]. Clinvar id is 1181620.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCD4	NM_005050.4	c.-226G>A		upstream_gene_variant		ENST00000356924.9	NP_005041.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCD4	ENST00000356924.9	c.-226G>A		upstream_gene_variant		1	NM_005050.4	ENSP00000349396.4

Frequencies

GnomAD3 genomes AF: 0.296 AC: 45080 AN: 152098 Hom.: 7265 Cov.: 33

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.355

GnomAD4 exome AF: 0.342 AC: 98460 AN: 287662 Hom.: 17711 Cov.: 3 AF XY: 0.345 AC XY: 50917 AN XY: 147536

Gnomad4 AFR exome AF: 0.168

Gnomad4 AMR exome AF: 0.256

Gnomad4 ASJ exome AF: 0.433

Gnomad4 EAS exome AF: 0.239

Gnomad4 SAS exome AF: 0.361

Gnomad4 FIN exome AF: 0.294

Gnomad4 NFE exome AF: 0.366

Gnomad4 OTH exome AF: 0.348

GnomAD4 genome AF: 0.296 AC: 45072 AN: 152216 Hom.: 7257 Cov.: 33 AF XY: 0.294 AC XY: 21868 AN XY: 74420

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.299

Gnomad4 ASJ AF: 0.425

Gnomad4 EAS AF: 0.251

Gnomad4 SAS AF: 0.359

Gnomad4 FIN AF: 0.292

Gnomad4 NFE AF: 0.362

Gnomad4 OTH AF: 0.356

Alfa AF: 0.298 Hom.: 1040

Bravo AF: 0.288

Asia WGS AF: 0.306 AC: 1062 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 29, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.5
DANN	Benign	0.82

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs17782508; hg19: chr14-74769841;