chr17-8039264-C-T

Variant names:

• chr17-8039264-C-T
• rs577729599
• NM_001141.3:c.109C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001141.3(ALOX15B):​c.109C>T​(p.Pro37Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000564 in 1,595,376 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000049 (0 hom.)
• Consequence: ALOX15B NM_001141.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0160
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.050696403).

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.109C>T	p.Pro37Ser	missense	Exon 1 of 14	NP_001132.2	O15296-1
	ALOX15B	NM_001039130.2		c.109C>T	p.Pro37Ser	missense	Exon 1 of 13	NP_001034219.1	O15296-4
	ALOX15B	NM_001039131.2		c.109C>T	p.Pro37Ser	missense	Exon 1 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.109C>T	p.Pro37Ser	missense	Exon 1 of 14	ENSP00000369530.4	O15296-1
	ALOX15B	ENST00000380173.6	TSL:1	c.109C>T	p.Pro37Ser	missense	Exon 1 of 13	ENSP00000369520.2	O15296-4
	ALOX15B	ENST00000573359.1	TSL:1	c.109C>T	p.Pro37Ser	missense	Exon 1 of 12	ENSP00000460332.2	O15296-2

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152234 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: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000215 AC: 5 AN: 232262 AF XY: 0.0000161

Gnomad AFR exome AF: 0.0000621

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000220

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000485 AC: 7 AN: 1443024 Hom.: 0 Cov.: 45 AF XY: 0.00000698 AC XY: 5 AN XY: 715880

African (AFR) AF: 0.00 AC: 0 AN: 33198

American (AMR) AF: 0.00 AC: 0 AN: 43056

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24496

East Asian (EAS) AF: 0.0000758 AC: 3 AN: 39558

South Asian (SAS) AF: 0.00 AC: 0 AN: 82828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52576

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5634

European-Non Finnish (NFE) AF: 0.00000363 AC: 4 AN: 1102112

Other (OTH) AF: 0.00 AC: 0 AN: 59566

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152352 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74502

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000241 AC: 1 AN: 41574

American (AMR) AF: 0.00 AC: 0 AN: 15310

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

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2114

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00000000770867), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.0000189

ExAC AF: 0.0000330 AC: 4

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	0.10
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0010	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		-0.016
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.97	N
REVEL	Benign	0.095
Sift	Benign	0.88	T
Sift4G	Benign	0.41	T
Polyphen		0.16	B
Vest4		0.13
MVP		0.76
MPC		0.30
ClinPred		0.057	T
GERP RS		3.3
PromoterAI		-0.014	Neutral
Varity_R		0.17
gMVP		0.34
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: rs577729599; hg19: chr17-7942582;