Genetic Variant NM_001140.5:c.1455A>G (chr17-4632946-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001140.5(ALOX15):c.1455A>G(p.Thr485Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,614,058 control chromosomes in the GnomAD database, including 9,366 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.078 ( 622 hom., cov: 32)

Exomes 𝑓: 0.11 ( 8744 hom. )

Consequence

ALOX15
NM_001140.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.24

Variant links:

Genes affected

ALOX15 (HGNC:433): (arachidonate 15-lipoxygenase) This gene encodes a member of the lipoxygenase family of proteins. The encoded enzyme acts on various polyunsaturated fatty acid substrates to generate various bioactive lipid mediators such as eicosanoids, hepoxilins, lipoxins, and other molecules. The encoded enzyme and its reaction products have been shown to regulate inflammation and immunity. Multiple pseudogenes of this gene have been identified in the human genome. [provided by RefSeq, Aug 2017]

ALOX15 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP7

Synonymous conserved (PhyloP=-4.24 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX15	NM_001140.5 link	c.1455A>G	p.Thr485Thr	synonymous_variant	Exon 11 of 14	ENST00000293761.8	NP_001131.3	P16050-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ALOX15	ENST00000293761.8 link	c.1455A>G	p.Thr485Thr	synonymous_variant	Exon 11 of 14	1	NM_001140.5	ENSP00000293761.3	P16050-1
ALOX15	ENST00000570836.6 link	c.1455A>G	p.Thr485Thr	synonymous_variant	Exon 12 of 15	2		ENSP00000458832.1	P16050-1
ALOX15	ENST00000574640.1 link	c.1338A>G	p.Thr446Thr	synonymous_variant	Exon 11 of 14	2		ENSP00000460483.1	P16050-2

Frequencies

GnomAD3 genomes

AF:

0.0786

AC:

11949

AN:

152068

Hom.:

623

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0198

Gnomad AMI

AF:

0.118

Gnomad AMR

AF:

0.0696

Gnomad ASJ

AF:

0.121

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0596

Gnomad FIN

AF:

0.0959

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.118

Gnomad OTH

AF:

0.0746

GnomAD3 exomes

AF:

0.0846

AC:

21281

AN:

251444

Hom.:

1150

AF XY:

0.0875

AC XY:

11891

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.0172

Gnomad AMR exome

AF:

0.0527

Gnomad ASJ exome

AF:

0.125

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.0622

Gnomad FIN exome

AF:

0.0955

Gnomad NFE exome

AF:

0.117

Gnomad OTH exome

AF:

0.0978

GnomAD4 exome

AF:

0.105

AC:

153903

AN:

1461872

Hom.:

8744

Cov.:

AF XY:

0.105

AC XY:

76332

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.0171

Gnomad4 AMR exome

AF:

0.0555

Gnomad4 ASJ exome

AF:

0.121

Gnomad4 EAS exome

AF:

0.000227

Gnomad4 SAS exome

AF:

0.0623

Gnomad4 FIN exome

AF:

0.0918

Gnomad4 NFE exome

AF:

0.117

Gnomad4 OTH exome

AF:

0.101

GnomAD4 genome

AF:

0.0785

AC:

11945

AN:

152186

Hom.:

622

Cov.:

AF XY:

0.0776

AC XY:

5772

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.0198

Gnomad4 AMR

AF:

0.0695

Gnomad4 ASJ

AF:

0.121

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.0591

Gnomad4 FIN

AF:

0.0959

Gnomad4 NFE

AF:

0.118

Gnomad4 OTH

AF:

0.0738

Alfa

AF:

0.109

Hom.:

1315

Bravo

AF:

0.0741

Asia WGS

AF:

0.0220

AC:

AN:

3478

EpiCase

AF:

0.130

EpiControl

AF:

0.131

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.84

DANN

Benign

0.43

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over