Variant chr17-75942258-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_004035.7(ACOX1):c.*4490A>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 0.124 in 149,176 control chromosomes in the GnomAD database, including 1,699 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1699 hom., cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ACOX1
NM_004035.7 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.52

Variant links:

Genes affected

ACOX1 (HGNC:119): (acyl-CoA oxidase 1) The protein encoded by this gene is the first enzyme of the fatty acid beta-oxidation pathway, which catalyzes the desaturation of acyl-CoAs to 2-trans-enoyl-CoAs. It donates electrons directly to molecular oxygen, thereby producing hydrogen peroxide. Defects in this gene result in pseudoneonatal adrenoleukodystrophy, a disease that is characterized by accumulation of very long chain fatty acids. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACOX1 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 (BayesDel_noAF=-1.04).

BP6

Variant 17-75942258-T-C is Benign according to our data. Variant chr17-75942258-T-C is described in ClinVar as [Benign]. Clinvar id is 325305.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACOX1	NM_004035.7 linkuse as main transcript	c.*4490A>G		3_prime_UTR_variant	14/14	ENST00000293217.10	NP_004026.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACOX1	ENST00000293217.10 linkuse as main transcript	c.*4490A>G		3_prime_UTR_variant	14/14	1	NM_004035.7	ENSP00000293217	A1	Q15067-2
ACOX1	ENST00000301608.9 linkuse as main transcript	c.*4490A>G		3_prime_UTR_variant	14/14	1		ENSP00000301608	P3	Q15067-1

Frequencies

GnomAD3 genomes

AF:

0.123

AC:

18405

AN:

149060

Hom.:

1695

Cov.:

show subpopulations

Gnomad AFR

AF:

0.262

Gnomad AMI

AF:

0.0235

Gnomad AMR

AF:

0.0837

Gnomad ASJ

AF:

0.0650

Gnomad EAS

AF:

0.0538

Gnomad SAS

AF:

0.148

Gnomad FIN

AF:

0.0428

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.0695

Gnomad OTH

AF:

0.116

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

Gnomad4 AFR exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.124

AC:

18430

AN:

149176

Hom.:

1699

Cov.:

AF XY:

0.122

AC XY:

8855

AN XY:

72832

show subpopulations

Gnomad4 AFR

AF:

0.262

Gnomad4 AMR

AF:

0.0834

Gnomad4 ASJ

AF:

0.0650

Gnomad4 EAS

AF:

0.0539

Gnomad4 SAS

AF:

0.148

Gnomad4 FIN

AF:

0.0428

Gnomad4 NFE

AF:

0.0695

Gnomad4 OTH

AF:

0.115

Alfa

AF:

0.108

Hom.:

169

Bravo

AF:

0.129

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Acyl-CoA oxidase deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.68

DANN

Benign

0.10

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