chr17-8044909-C-G

Variant names:

• chr17-8044909-C-G
• rs147889634
• NM_001141.3:c.757C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001141.3(ALOX15B):​c.757C>G​(p.Arg253Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R253C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ALOX15B NM_001141.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27

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 Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX15B	NM_001141.3	c.757C>G	p.Arg253Gly	missense_variant	Exon 6 of 14	ENST00000380183.9	NP_001132.2
ALOX15B	NM_001039130.2	c.757C>G	p.Arg253Gly	missense_variant	Exon 6 of 13		NP_001034219.1
ALOX15B	NM_001039131.2	c.757C>G	p.Arg253Gly	missense_variant	Exon 6 of 12		NP_001034220.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX15B	ENST00000380183.9	c.757C>G	p.Arg253Gly	missense_variant	Exon 6 of 14	1	NM_001141.3	ENSP00000369530.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461880 Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.034	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	15
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T;D;.;.
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.089	N
LIST_S2	Benign	0.68	T;T;T;T
M_CAP	Benign	0.077	D
MetaRNN	Uncertain	0.63	D;D;D;D
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Uncertain	2.6	M;.;M;M
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-4.2	D;.;D;.
REVEL	Uncertain	0.41
Sift	Benign	0.089	T;.;T;.
Sift4G	Benign	0.072	T;T;T;T
Polyphen		0.42	B;.;B;B
Vest4		0.25
MutPred		0.76		Loss of stability (P = 0.0287);Loss of stability (P = 0.0287);Loss of stability (P = 0.0287);Loss of stability (P = 0.0287);
MVP		0.96
MPC		0.57
ClinPred		0.74	D
GERP RS		1.8
Varity_R		0.55
gMVP		0.89

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

Publications

LitVar

Other links and lift over

dbSNP: rs147889634; hg19: chr17-7948227;