17-4631740-G-A

Position:

• chr17-4631740-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000293761.8(ALOX15):​c.1849C>T​(p.Pro617Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0122 in 1,614,068 control chromosomes in the GnomAD database, including 841 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (96 hom., cov: 32)
  • Exomes 𝑓: 0.012 (745 hom.)
• Consequence: ALOX15 ENST00000293761.8 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0300

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.001753509).
• BP6: Variant 17-4631740-G-A is Benign according to our data. Variant chr17-4631740-G-A is described in ClinVar as [Benign]. Clinvar id is 1225468.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0983 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALOX15	NM_001140.5	c.1849C>T	p.Pro617Ser	missense_variant	14/14	ENST00000293761.8	NP_001131.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALOX15	ENST00000293761.8	c.1849C>T	p.Pro617Ser	missense_variant	14/14	1	NM_001140.5	ENSP00000293761	P1
ALOX15	ENST00000570836.6	c.1849C>T	p.Pro617Ser	missense_variant	15/15	2		ENSP00000458832	P1
ALOX15	ENST00000574640.1	c.1732C>T	p.Pro578Ser	missense_variant	14/14	2		ENSP00000460483

Frequencies

GnomAD3 genomes AF: 0.0142 AC: 2167 AN: 152130 Hom.: 93 Cov.: 32

Gnomad AFR AF: 0.00261

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0762

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.00347

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.00425

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00366

Gnomad OTH AF: 0.0211

GnomAD3 exomes AF: 0.0271 AC: 6800 AN: 250728 Hom.: 314 AF XY: 0.0286 AC XY: 3879 AN XY: 135560

Gnomad AFR exome AF: 0.00191

Gnomad AMR exome AF: 0.0796

Gnomad ASJ exome AF: 0.00457

Gnomad EAS exome AF: 0.00201

Gnomad SAS exome AF: 0.105

Gnomad FIN exome AF: 0.00334

Gnomad NFE exome AF: 0.00437

Gnomad OTH exome AF: 0.0235

GnomAD4 exome AF: 0.0120 AC: 17573 AN: 1461820 Hom.: 745 Cov.: 33 AF XY: 0.0144 AC XY: 10486 AN XY: 727216

Gnomad4 AFR exome AF: 0.00179

Gnomad4 AMR exome AF: 0.0803

Gnomad4 ASJ exome AF: 0.00478

Gnomad4 EAS exome AF: 0.00161

Gnomad4 SAS exome AF: 0.101

Gnomad4 FIN exome AF: 0.00304

Gnomad4 NFE exome AF: 0.00349

Gnomad4 OTH exome AF: 0.0148

GnomAD4 genome AF: 0.0143 AC: 2180 AN: 152248 Hom.: 96 Cov.: 32 AF XY: 0.0178 AC XY: 1323 AN XY: 74432

Gnomad4 AFR AF: 0.00260

Gnomad4 AMR AF: 0.0767

Gnomad4 ASJ AF: 0.00576

Gnomad4 EAS AF: 0.00328

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.00425

Gnomad4 NFE AF: 0.00366

Gnomad4 OTH AF: 0.0237

Alfa AF: 0.00542 Hom.: 27

Bravo AF: 0.0158

TwinsUK AF: 0.00243 AC: 9

ALSPAC AF: 0.00285 AC: 11

ESP6500AA AF: 0.00272 AC: 12

ESP6500EA AF: 0.00372 AC: 32

ExAC AF: 0.0258 AC: 3132

Asia WGS AF: 0.0650 AC: 227 AN: 3478

EpiCase AF: 0.00420

EpiControl AF: 0.00545

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 16, 2019	This variant is associated with the following publications: (PMID: 29669943) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	13
DANN	Benign	0.97
DEOGEN2	Uncertain	0.60	D;D;.
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.80	.;T;T
MetaRNN	Benign	0.0018	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M;M;.
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-2.5	.;N;.
REVEL	Benign	0.062
Sift	Benign	0.059	.;T;.
Sift4G	Benign	0.073	T;T;T
Polyphen		0.32	B;B;.
Vest4		0.036
MPC		0.21
ClinPred		0.0068	T
GERP RS		1.7
Varity_R		0.099
gMVP		0.25

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: rs41432647; hg19: chr17-4535035;