17-8042407-A-G

Variant names:

• chr17-8042407-A-G
• rs139800287
• NM_001141.3:c.488A>G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001141.3(ALOX15B):​c.488A>G​(p.Asp163Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00162 in 1,614,110 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D163E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (2 hom.)
• Consequence: ALOX15B NM_001141.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.31

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

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0060354173).
• BP6: Variant 17-8042407-A-G is Benign according to our data. Variant chr17-8042407-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 711528.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX15B	NM_001141.3	c.488A>G	p.Asp163Gly	missense_variant	Exon 4 of 14	ENST00000380183.9	NP_001132.2
ALOX15B	NM_001039130.2	c.488A>G	p.Asp163Gly	missense_variant	Exon 4 of 13		NP_001034219.1
ALOX15B	NM_001039131.2	c.488A>G	p.Asp163Gly	missense_variant	Exon 4 of 12		NP_001034220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX15B	ENST00000380183.9	c.488A>G	p.Asp163Gly	missense_variant	Exon 4 of 14	1	NM_001141.3	ENSP00000369530.4

Frequencies

GnomAD3 genomes AF: 0.00160 AC: 243 AN: 152208 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00160

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00212

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.00134 AC: 336 AN: 251428 Hom.: 0 AF XY: 0.00136 AC XY: 185 AN XY: 135886

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.000434

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00121

Gnomad FIN exome AF: 0.00291

Gnomad NFE exome AF: 0.00186

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.00162 AC: 2375 AN: 1461784 Hom.: 2 Cov.: 32 AF XY: 0.00160 AC XY: 1164 AN XY: 727190

Gnomad4 AFR exome AF: 0.000179

Gnomad4 AMR exome AF: 0.000358

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00132

Gnomad4 FIN exome AF: 0.00354

Gnomad4 NFE exome AF: 0.00179

Gnomad4 OTH exome AF: 0.000911

GnomAD4 genome AF: 0.00160 AC: 243 AN: 152326 Hom.: 0 Cov.: 32 AF XY: 0.00164 AC XY: 122 AN XY: 74492

Gnomad4 AFR AF: 0.000337

Gnomad4 AMR AF: 0.000457

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00160

Gnomad4 NFE AF: 0.00212

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.00187 Hom.: 2

Bravo AF: 0.00168

TwinsUK AF: 0.00216 AC: 8

ALSPAC AF: 0.00130 AC: 5

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00291 AC: 25

ExAC AF: 0.00133 AC: 161

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00191

EpiControl AF: 0.00119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 31, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.026	T;T;.;.
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.79	T;T;T;T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.0060	T;T;T;T
MetaSVM	Uncertain	0.045	D
MutationAssessor	Uncertain	2.5	M;.;M;M
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-3.4	D;.;D;.
REVEL	Uncertain	0.39
Sift	Benign	0.038	D;.;D;.
Sift4G	Uncertain	0.044	D;D;D;D
Polyphen		0.0050	B;.;B;B
Vest4		0.22
MVP		0.85
MPC		0.20
ClinPred		0.031	T
GERP RS		4.4
Varity_R		0.27
gMVP		0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs139800287; hg19: chr17-7945725;