chr17-8042407-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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. 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
• Publications: 8 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: Benign. The variant received -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 VariationId is 711528.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

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.488A>G	p.Asp163Gly	missense	Exon 4 of 14	NP_001132.2	O15296-1
	ALOX15B	NM_001039130.2		c.488A>G	p.Asp163Gly	missense	Exon 4 of 13	NP_001034219.1	O15296-4
	ALOX15B	NM_001039131.2		c.488A>G	p.Asp163Gly	missense	Exon 4 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.488A>G	p.Asp163Gly	missense	Exon 4 of 14	ENSP00000369530.4	O15296-1
	ALOX15B	ENST00000380173.6	TSL:1	c.488A>G	p.Asp163Gly	missense	Exon 4 of 13	ENSP00000369520.2	O15296-4
	ALOX15B	ENST00000573359.1	TSL:1	c.488A>G	p.Asp163Gly	missense	Exon 4 of 12	ENSP00000460332.2	O15296-2

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

GnomAD2 exomes AF: 0.00134 AC: 336 AN: 251428 AF XY: 0.00136

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 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

African (AFR) AF: 0.000179 AC: 6 AN: 33476

American (AMR) AF: 0.000358 AC: 16 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00132 AC: 114 AN: 86256

European-Finnish (FIN) AF: 0.00354 AC: 189 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 0.00179 AC: 1995 AN: 1111994

Other (OTH) AF: 0.000911 AC: 55 AN: 60388

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

African (AFR) AF: 0.000337 AC: 14 AN: 41578

American (AMR) AF: 0.000457 AC: 7 AN: 15306

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4826

European-Finnish (FIN) AF: 0.00160 AC: 17 AN: 10622

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

European-Non Finnish (NFE) AF: 0.00212 AC: 144 AN: 68014

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.00169 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

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.79	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.0060	T
MetaSVM	Uncertain	0.045	D
MutationAssessor	Uncertain	2.5	M
PhyloP100		1.3
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-3.4	D
REVEL	Uncertain	0.39
Sift	Benign	0.038	D
Sift4G	Uncertain	0.044	D
Polyphen		0.0050	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
Mutation Taster		=66/34	polymorphism

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

Other links and lift over

dbSNP: rs139800287; hg19: chr17-7945725;