2-200605631-G-A

Variant summary

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

The NM_001159.4(AOX1):c.907+3G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0052 in 1,423,636 control chromosomes in the GnomAD database, including 331 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.027 (193 hom., cov: 32)
  • Exomes 𝑓: 0.0025 (138 hom.)
• Consequence: AOX1 NM_001159.4 splice_donor_region, intron
• Scores: Splicing: ADA: 0.00002854
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.131

Genes affected

AOX1 (HGNC:553): (aldehyde oxidase 1) Aldehyde oxidase produces hydrogen peroxide and, under certain conditions, can catalyze the formation of superoxide. Aldehyde oxidase is a candidate gene for amyotrophic lateral sclerosis. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 2-200605631-G-A is Benign according to our data. Variant chr2-200605631-G-A is described in ClinVar as [Benign]. Clinvar id is 767839.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0934 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AOX1	NM_001159.4	c.907+3G>A		splice_donor_region_variant, intron_variant		ENST00000374700.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AOX1	ENST00000374700.7	c.907+3G>A		splice_donor_region_variant, intron_variant		1	NM_001159.4	P1

Frequencies

GnomAD3 genomes AF: 0.0273 AC: 4143 AN: 151720 Hom.: 191 Cov.: 32

Gnomad AFR AF: 0.0957

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00841

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000324

Gnomad OTH AF: 0.0187

GnomAD3 exomes AF: 0.00697 AC: 1301 AN: 186618 Hom.: 57 AF XY: 0.00513 AC XY: 528 AN XY: 102922

Gnomad AFR exome AF: 0.0954

Gnomad AMR exome AF: 0.00380

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000388

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000238

Gnomad OTH exome AF: 0.00300

GnomAD4 exome AF: 0.00255 AC: 3239 AN: 1271796 Hom.: 138 Cov.: 18 AF XY: 0.00234 AC XY: 1481 AN XY: 633500

Gnomad4 AFR exome AF: 0.0988

Gnomad4 AMR exome AF: 0.00475

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000398

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000131

Gnomad4 OTH exome AF: 0.00495

GnomAD4 genome AF: 0.0274 AC: 4159 AN: 151840 Hom.: 193 Cov.: 32 AF XY: 0.0267 AC XY: 1979 AN XY: 74182

Gnomad4 AFR AF: 0.0958

Gnomad4 AMR AF: 0.00839

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000623

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000324

Gnomad4 OTH AF: 0.0185

Alfa AF: 0.0130 Hom.: 50

Bravo AF: 0.0308

Asia WGS AF: 0.00462 AC: 17 AN: 3474

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

Invitae

Aug 17, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
Cadd	Benign	6.9
Dann	Benign	0.46

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000029
dbscSNV1_RF	Benign	0.0
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: rs73049078; hg19: chr2-201470354;