17-8039489-C-G

Variant names:

• chr17-8039489-C-G
• rs200065292
• NM_001141.3:c.251C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001141.3(ALOX15B):​c.251C>G​(p.Pro84Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000777 in 1,583,108 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00045 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000038 (0 hom.)
• Consequence: ALOX15B NM_001141.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.67
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0163365).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001141.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALOX15B	NM_001141.3	MANE Select	c.251C>G	p.Pro84Arg	missense	Exon 2 of 14	NP_001132.2	O15296-1
	ALOX15B	NM_001039130.2		c.251C>G	p.Pro84Arg	missense	Exon 2 of 13	NP_001034219.1	O15296-4
	ALOX15B	NM_001039131.2		c.251C>G	p.Pro84Arg	missense	Exon 2 of 12	NP_001034220.1	O15296-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALOX15B	ENST00000380183.9	TSL:1 MANE Select	c.251C>G	p.Pro84Arg	missense	Exon 2 of 14	ENSP00000369530.4	O15296-1
	ALOX15B	ENST00000380173.6	TSL:1	c.251C>G	p.Pro84Arg	missense	Exon 2 of 13	ENSP00000369520.2	O15296-4
	ALOX15B	ENST00000573359.1	TSL:1	c.251C>G	p.Pro84Arg	missense	Exon 2 of 12	ENSP00000460332.2	O15296-2

Frequencies

GnomAD3 genomes AF: 0.000453 AC: 69 AN: 152190 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00162

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000122 AC: 23 AN: 188382 AF XY: 0.0000865

Gnomad AFR exome AF: 0.00185

Gnomad AMR exome AF: 0.0000990

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000706

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000377 AC: 54 AN: 1430918 Hom.: 0 Cov.: 45 AF XY: 0.0000324 AC XY: 23 AN XY: 710138

African (AFR) AF: 0.00111 AC: 36 AN: 32528

American (AMR) AF: 0.0000959 AC: 4 AN: 41712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25548

East Asian (EAS) AF: 0.0000266 AC: 1 AN: 37612

South Asian (SAS) AF: 0.00 AC: 0 AN: 83200

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46742

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5542

European-Non Finnish (NFE) AF: 0.00000273 AC: 3 AN: 1098902

Other (OTH) AF: 0.000169 AC: 10 AN: 59132

GnomAD4 genome AF: 0.000453 AC: 69 AN: 152190 Hom.: 0 Cov.: 33 AF XY: 0.000350 AC XY: 26 AN XY: 74354

African (AFR) AF: 0.00162 AC: 67 AN: 41444

American (AMR) AF: 0.0000654 AC: 1 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.000478 AC: 1 AN: 2090

Alfa AF: 0.000569 Hom.: 0

Bravo AF: 0.000499

ESP6500AA AF: 0.000469 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000127 AC: 15

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.73
DANN	Benign	0.69
DEOGEN2	Benign	0.00067	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.045	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.016	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.68	N
PhyloP100		-1.7
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.026
Sift	Benign	0.26	T
Sift4G	Benign	0.47	T
Polyphen		0.0030	B
Vest4		0.043
MVP		0.41
MPC		0.16
ClinPred		0.0067	T
GERP RS		-4.1
PromoterAI		-0.15	Neutral
Varity_R		0.060
gMVP		0.23
Mutation Taster		=100/0	polymorphism

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: rs200065292; hg19: chr17-7942807;