rs11651351

chr17-75970781-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004035.7(ACOX1):c.269+7753G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0435 in 152,208 control chromosomes in the GnomAD database, including 194 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.043 (194 hom., cov: 32)
• Consequence: ACOX1 NM_004035.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.120

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACOX1	NM_004035.7	c.269+7753G>A		intron_variant		ENST00000293217.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACOX1	ENST00000293217.10	c.269+7753G>A		intron_variant		1	NM_004035.7	A1

Frequencies

GnomAD3 genomes AF: 0.0435 AC: 6617 AN: 152090 Hom.: 194 Cov.: 32

Gnomad AFR AF: 0.0263

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.0429

Gnomad ASJ AF: 0.0254

Gnomad EAS AF: 0.00808

Gnomad SAS AF: 0.0303

Gnomad FIN AF: 0.0323

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0606

Gnomad OTH AF: 0.0445

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0435 AC: 6621 AN: 152208 Hom.: 194 Cov.: 32 AF XY: 0.0416 AC XY: 3097 AN XY: 74420

Gnomad4 AFR AF: 0.0263

Gnomad4 AMR AF: 0.0428

Gnomad4 ASJ AF: 0.0254

Gnomad4 EAS AF: 0.00810

Gnomad4 SAS AF: 0.0307

Gnomad4 FIN AF: 0.0323

Gnomad4 NFE AF: 0.0606

Gnomad4 OTH AF: 0.0445

Alfa AF: 0.0547 Hom.: 368

Bravo AF: 0.0442

Asia WGS AF: 0.0270 AC: 94 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
Cadd	Benign	6.1
Dann	Benign	0.88

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: rs11651351; hg19: chr17-73966862;