17-8039506-C-G

Variant names:

• chr17-8039506-C-G
• rs368311556
• NM_001141.3:c.268C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001141.3(ALOX15B):​c.268C>G​(p.Arg90Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000705 in 1,417,932 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R90C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: ALOX15B NM_001141.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.121
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3920226).

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.268C>G	p.Arg90Gly	missense	Exon 2 of 14	NP_001132.2	O15296-1
	ALOX15B	NM_001039130.2		c.268C>G	p.Arg90Gly	missense	Exon 2 of 13	NP_001034219.1	O15296-4
	ALOX15B	NM_001039131.2		c.268C>G	p.Arg90Gly	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.268C>G	p.Arg90Gly	missense	Exon 2 of 14	ENSP00000369530.4	O15296-1
	ALOX15B	ENST00000380173.6	TSL:1	c.268C>G	p.Arg90Gly	missense	Exon 2 of 13	ENSP00000369520.2	O15296-4
	ALOX15B	ENST00000573359.1	TSL:1	c.268C>G	p.Arg90Gly	missense	Exon 2 of 12	ENSP00000460332.2	O15296-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.05e-7 AC: 1 AN: 1417932 Hom.: 0 Cov.: 47 AF XY: 0.00 AC XY: 0 AN XY: 702758

African (AFR) AF: 0.00 AC: 0 AN: 32216

American (AMR) AF: 0.00 AC: 0 AN: 40082

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25382

East Asian (EAS) AF: 0.00 AC: 0 AN: 36938

South Asian (SAS) AF: 0.00 AC: 0 AN: 82158

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5440

European-Non Finnish (NFE) AF: 9.15e-7 AC: 1 AN: 1092594

Other (OTH) AF: 0.00 AC: 0 AN: 58722

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		-0.12
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.13
Sift	Benign	0.065	T
Sift4G	Benign	0.11	T
Polyphen		0.69	P
Vest4		0.45
MutPred		0.70		Gain of catalytic residue at W91 (P = 0.0634)
MVP		0.24
MPC		0.68
ClinPred		0.72	D
GERP RS		0.79
PromoterAI		0.0066	Neutral
Varity_R		0.31
gMVP		0.37

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: rs368311556; hg19: chr17-7942824;