chr17-8047001-G-A

Position:

• chr17-8047001-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001141.3(ALOX15B):​c.1382G>A​(p.Arg461Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00228 in 1,614,084 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.0017 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (23 hom.)
• Consequence: ALOX15B NM_001141.3 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: -0.838

Genes affected

ALOX15B (HGNC:434): (arachidonate 15-lipoxygenase type B) This gene encodes a member of the lipoxygenase family of structurally related nonheme iron dioxygenases involved in the production of fatty acid hydroperoxides. The encoded protein converts arachidonic acid exclusively to 15S-hydroperoxyeicosatetraenoic acid, while metabolizing linoleic acid less effectively. This gene is located in a cluster of related genes and a pseudogene that spans approximately 100 kilobases on the short arm of chromosome 17. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

ALOX15B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004040092).
• BS2: High Homozygotes in GnomAdExome4 at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALOX15B	NM_001141.3	c.1382G>A	p.Arg461Gln	missense_variant	10/14	ENST00000380183.9	NP_001132.2
ALOX15B	NM_001039130.2	c.1295G>A	p.Arg432Gln	missense_variant	9/13		NP_001034219.1
ALOX15B	NM_001039131.2	c.1295G>A	p.Arg432Gln	missense_variant	9/12		NP_001034220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALOX15B	ENST00000380183.9	c.1382G>A	p.Arg461Gln	missense_variant	10/14	1	NM_001141.3	ENSP00000369530.4

Frequencies

GnomAD3 genomes AF: 0.00168 AC: 256 AN: 152096 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0157

Gnomad FIN AF: 0.000660

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00185

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00352 AC: 885 AN: 251464 Hom.: 6 AF XY: 0.00419 AC XY: 570 AN XY: 135908

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00147

Gnomad ASJ exome AF: 0.00595

Gnomad EAS exome AF: 0.000217

Gnomad SAS exome AF: 0.0151

Gnomad FIN exome AF: 0.000786

Gnomad NFE exome AF: 0.00229

Gnomad OTH exome AF: 0.00472

GnomAD4 exome AF: 0.00235 AC: 3431 AN: 1461870 Hom.: 23 Cov.: 32 AF XY: 0.00276 AC XY: 2004 AN XY: 727238

Gnomad4 AFR exome AF: 0.0000597

Gnomad4 AMR exome AF: 0.00145

Gnomad4 ASJ exome AF: 0.00627

Gnomad4 EAS exome AF: 0.000378

Gnomad4 SAS exome AF: 0.0151

Gnomad4 FIN exome AF: 0.000655

Gnomad4 NFE exome AF: 0.00140

Gnomad4 OTH exome AF: 0.00326

GnomAD4 genome AF: 0.00168 AC: 256 AN: 152214 Hom.: 0 Cov.: 32 AF XY: 0.00200 AC XY: 149 AN XY: 74428

Gnomad4 AFR AF: 0.000217

Gnomad4 AMR AF: 0.00118

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0157

Gnomad4 FIN AF: 0.000660

Gnomad4 NFE AF: 0.00185

Gnomad4 OTH AF: 0.00332

Alfa AF: 0.00219 Hom.: 1

Bravo AF: 0.00172

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.00156 AC: 6

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00221 AC: 19

ExAC AF: 0.00373 AC: 453

Asia WGS AF: 0.00491 AC: 17 AN: 3478

EpiCase AF: 0.00322

EpiControl AF: 0.00362

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Uncertain:2

Uncertain significance, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Genomic Research Center, Shahid Beheshti University of Medical Sciences	Aug 07, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	8.9
DANN	Benign	0.93
DEOGEN2	Benign	0.037	T;T;.;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.68	T;T;T;T
MetaRNN	Benign	0.0040	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;.;.;.
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.84	N;.;N;.
REVEL	Benign	0.13
Sift	Benign	0.55	T;.;T;.
Sift4G	Benign	0.80	T;T;T;T
Polyphen		0.047	B;.;B;B
Vest4		0.047
MVP		0.83
MPC		0.18
ClinPred		0.0088	T
GERP RS		-1.1
Varity_R		0.18
gMVP		0.13

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs140623478; hg19: chr17-7950319;