17-8039450-A-T

Variant names:

• chr17-8039450-A-T
• rs776161988
• NM_001141.3:c.212A>T

Variant summary

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

The NM_001141.3(ALOX15B):​c.212A>T​(p.Lys71Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000112 in 1,608,506 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: ALOX15B NM_001141.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.44
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.212A>T	p.Lys71Met	missense	Exon 2 of 14	NP_001132.2	O15296-1
	ALOX15B	NM_001039130.2		c.212A>T	p.Lys71Met	missense	Exon 2 of 13	NP_001034219.1	O15296-4
	ALOX15B	NM_001039131.2		c.212A>T	p.Lys71Met	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.212A>T	p.Lys71Met	missense	Exon 2 of 14	ENSP00000369530.4	O15296-1
	ALOX15B	ENST00000380173.6	TSL:1	c.212A>T	p.Lys71Met	missense	Exon 2 of 13	ENSP00000369520.2	O15296-4
	ALOX15B	ENST00000573359.1	TSL:1	c.212A>T	p.Lys71Met	missense	Exon 2 of 12	ENSP00000460332.2	O15296-2

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152178 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

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: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000128 AC: 3 AN: 233636 AF XY: 0.0000156

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: 0.0000288

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000961 AC: 14 AN: 1456328 Hom.: 0 Cov.: 45 AF XY: 0.00000828 AC XY: 6 AN XY: 724262

African (AFR) AF: 0.00 AC: 0 AN: 33338

American (AMR) AF: 0.00 AC: 0 AN: 44326

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25968

East Asian (EAS) AF: 0.00 AC: 0 AN: 39418

South Asian (SAS) AF: 0.00 AC: 0 AN: 85582

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51644

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5704

European-Non Finnish (NFE) AF: 0.0000126 AC: 14 AN: 1110232

Other (OTH) AF: 0.00 AC: 0 AN: 60116

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152178 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74338

African (AFR) AF: 0.00 AC: 0 AN: 41442

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

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

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000826 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	Pathogenic	0.56
BayesDel_addAF	Uncertain	0.030	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.62	D
MetaSVM	Uncertain	-0.13	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		4.4
PrimateAI	Uncertain	0.73	T
PROVEAN	Pathogenic	-5.1	D
REVEL	Uncertain	0.47
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.53
MVP		0.76
MPC		0.69
ClinPred		1.0	D
GERP RS		2.9
PromoterAI		-0.043	Neutral
Varity_R		0.69
gMVP		0.71
Mutation Taster		=59/41	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs776161988; hg19: chr17-7942768;