rs6795193

Variant names:

• chr3-58512052-C-T
• rs6795193
• NM_003500.4:c.1851-3027G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003500.4(ACOX2):​c.1851-3027G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 152,090 control chromosomes in the GnomAD database, including 6,372 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 0.28 (6372 hom., cov: 32)
• Consequence: ACOX2 NM_003500.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.169
• Publications: 8 publications found

Genes affected

ACOX2 (HGNC:120): (acyl-CoA oxidase 2) The product of this gene belongs to the acyl-CoA oxidase family. It encodes the branched-chain acyl-CoA oxidase which is involved in the degradation of long branched fatty acids and bile acid intermediates in peroxisomes. Deficiency of this enzyme results in the accumulation of branched fatty acids and bile acid intermediates, and may lead to Zellweger syndrome, severe cognitive disability, and death in children. [provided by RefSeq, Mar 2009]

ACOX2 Gene-Disease associations (from GenCC):

• congenital bile acid synthesis defect 6

  Inheritance: AR Classification: MODERATE, LIMITED Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACOX2	NM_003500.4	c.1851-3027G>A		intron_variant	Intron 13 of 14	ENST00000302819.10	NP_003491.1
ACOX2	XM_047449042.1	c.2049-3027G>A		intron_variant	Intron 13 of 14		XP_047304998.1
ACOX2	XM_005265505.2	c.1851-3027G>A		intron_variant	Intron 13 of 14		XP_005265562.1
ACOX2	XM_006713340.4	c.1557-3027G>A		intron_variant	Intron 12 of 13		XP_006713403.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACOX2	ENST00000302819.10	c.1851-3027G>A		intron_variant	Intron 13 of 14	1	NM_003500.4	ENSP00000307697.5

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42531 AN: 151972 Hom.: 6369 Cov.: 32

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.00269

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.299

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

GnomAD4 genome AF: 0.280 AC: 42555 AN: 152090 Hom.: 6372 Cov.: 32 AF XY: 0.271 AC XY: 20119 AN XY: 74332

African (AFR) AF: 0.277 AC: 11466 AN: 41446

American (AMR) AF: 0.235 AC: 3597 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.418 AC: 1450 AN: 3472

East Asian (EAS) AF: 0.00270 AC: 14 AN: 5190

South Asian (SAS) AF: 0.200 AC: 967 AN: 4824

European-Finnish (FIN) AF: 0.213 AC: 2258 AN: 10580

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.320 AC: 21750 AN: 67976

Other (OTH) AF: 0.296 AC: 623 AN: 2106

Alfa AF: 0.318 Hom.: 13185

Bravo AF: 0.284

Asia WGS AF: 0.0990 AC: 348 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.4
DANN	Benign	0.83
PhyloP100		0.17
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6795193; hg19: chr3-58497779;