17-8039506-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001141.3(ALOX15B):​c.268C>T​(p.Arg90Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000803 in 1,570,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000081 (0 hom.)
• Consequence: ALOX15B NM_001141.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.121
• Publications: 2 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2537794).

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>T	p.Arg90Cys	missense	Exon 2 of 14	NP_001132.2	O15296-1
	ALOX15B	NM_001039130.2		c.268C>T	p.Arg90Cys	missense	Exon 2 of 13	NP_001034219.1	O15296-4
	ALOX15B	NM_001039131.2		c.268C>T	p.Arg90Cys	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>T	p.Arg90Cys	missense	Exon 2 of 14	ENSP00000369530.4	O15296-1
	ALOX15B	ENST00000380173.6	TSL:1	c.268C>T	p.Arg90Cys	missense	Exon 2 of 13	ENSP00000369520.2	O15296-4
	ALOX15B	ENST00000573359.1	TSL:1	c.268C>T	p.Arg90Cys	missense	Exon 2 of 12	ENSP00000460332.2	O15296-2

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152080 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000407 AC: 7 AN: 171830 AF XY: 0.0000421

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000991

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000811 AC: 115 AN: 1417932 Hom.: 0 Cov.: 47 AF XY: 0.0000811 AC XY: 57 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: 0.000104 AC: 114 AN: 1092594

Other (OTH) AF: 0.0000170 AC: 1 AN: 58722

GnomAD4 genome AF: 0.0000723 AC: 11 AN: 152080 Hom.: 0 Cov.: 33 AF XY: 0.0000673 AC XY: 5 AN XY: 74308

African (AFR) AF: 0.0000241 AC: 1 AN: 41418

American (AMR) AF: 0.00 AC: 0 AN: 15282

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

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

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 67992

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000595 Hom.: 0

Bravo AF: 0.0000567

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000121 AC: 1

ExAC AF: 0.00000855 AC: 1

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	0.11
BayesDel_addAF	Benign	-0.091	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.035	T
Eigen	Benign	0.0079
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.30	N
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		-0.12
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.23
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.025	D
Polyphen		1.0	D
Vest4		0.47
MVP		0.38
MPC		0.74
ClinPred		0.87	D
GERP RS		0.79
PromoterAI		-0.0081	Neutral
Varity_R		0.30
gMVP		0.42
Mutation Taster		=77/23	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: rs368311556; hg19: chr17-7942824; COSMIC: COSV101205543;