17-4633137-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001140.5(ALOX15):c.1418+9A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00251 in 1,613,020 control chromosomes in the GnomAD database, including 94 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.014 (52 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (42 hom.)
• Consequence: ALOX15 NM_001140.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.78

Genes affected

ALOX15 (HGNC:433): (arachidonate 15-lipoxygenase) This gene encodes a member of the lipoxygenase family of proteins. The encoded enzyme acts on various polyunsaturated fatty acid substrates to generate various bioactive lipid mediators such as eicosanoids, hepoxilins, lipoxins, and other molecules. The encoded enzyme and its reaction products have been shown to regulate inflammation and immunity. Multiple pseudogenes of this gene have been identified in the human genome. [provided by RefSeq, Aug 2017]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 17-4633137-T-C is Benign according to our data. Variant chr17-4633137-T-C is described in ClinVar as [Benign]. Clinvar id is 777095.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0137 (2090/152192) while in subpopulation AFR AF= 0.0483 (2008/41534). AF 95% confidence interval is 0.0466. There are 52 homozygotes in gnomad4. There are 1011 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 47 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALOX15	NM_001140.5	c.1418+9A>G		intron_variant		ENST00000293761.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALOX15	ENST00000293761.8	c.1418+9A>G		intron_variant		1	NM_001140.5	P1
ALOX15	ENST00000570836.6	c.1418+9A>G		intron_variant		2		P1
ALOX15	ENST00000574640.1	c.1301+9A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0136 AC: 2071 AN: 152074 Hom.: 47 Cov.: 32

Gnomad AFR AF: 0.0481

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00574

GnomAD3 exomes AF: 0.00365 AC: 913 AN: 250474 Hom.: 21 AF XY: 0.00268 AC XY: 363 AN XY: 135462

Gnomad AFR exome AF: 0.0505

Gnomad AMR exome AF: 0.00226

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000328

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000619

Gnomad OTH exome AF: 0.00164

GnomAD4 exome AF: 0.00134 AC: 1953 AN: 1460828 Hom.: 42 Cov.: 32 AF XY: 0.00119 AC XY: 863 AN XY: 726560

Gnomad4 AFR exome AF: 0.0475

Gnomad4 AMR exome AF: 0.00262

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000928

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000351

Gnomad4 OTH exome AF: 0.00316

GnomAD4 genome AF: 0.0137 AC: 2090 AN: 152192 Hom.: 52 Cov.: 32 AF XY: 0.0136 AC XY: 1011 AN XY: 74408

Gnomad4 AFR AF: 0.0483

Gnomad4 AMR AF: 0.00392

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00568

Alfa AF: 0.00838 Hom.: 18

Bravo AF: 0.0154

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000119

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

Jul 15, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.10
Dann	Benign	0.31

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: rs11568126; hg19: chr17-4536432;