10-45444169-A-C

Variant names:

• chr10-45444169-A-C
• rs2229136
• NM_000698.5:c.1728A>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_000698.5(ALOX5):​c.1728A>C​(p.Pro576Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000712 in 1,404,194 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: ALOX5 NM_000698.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.92
• Publications: 0 publications found

Genes affected

ALOX5 (HGNC:435): (arachidonate 5-lipoxygenase) This gene encodes a member of the lipoxygenase gene family and plays a dual role in the synthesis of leukotrienes from arachidonic acid. The encoded protein, which is expressed specifically in bone marrow-derived cells, catalyzes the conversion of arachidonic acid to 5(S)-hydroperoxy-6-trans-8,11,14-cis-eicosatetraenoic acid, and further to the allylic epoxide 5(S)-trans-7,9-trans-11,14-cis-eicosatetrenoic acid (leukotriene A4). Leukotrienes are important mediators of a number of inflammatory and allergic conditions. Mutations in the promoter region of this gene lead to a diminished response to antileukotriene drugs used in the treatment of asthma and may also be associated with atherosclerosis and several cancers. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP7: Synonymous conserved (PhyloP=-4.92 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000698.5. 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
	ALOX5	NM_000698.5	MANE Select	c.1728A>C	p.Pro576Pro	synonymous	Exon 13 of 14	NP_000689.1	P09917-1
	ALOX5	NM_001320861.2		c.1641A>C	p.Pro547Pro	synonymous	Exon 13 of 14	NP_001307790.1
	ALOX5	NM_001256153.3		c.1632A>C	p.Pro544Pro	synonymous	Exon 13 of 14	NP_001243082.1	P09917-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALOX5	ENST00000374391.7	TSL:1 MANE Select	c.1728A>C	p.Pro576Pro	synonymous	Exon 13 of 14	ENSP00000363512.2	P09917-1
	ALOX5	ENST00000542434.5	TSL:1	c.1674+341A>C		intron	N/A	ENSP00000437634.1	P09917-2
	ALOX5	ENST00000851643.1		c.1764A>C	p.Pro588Pro	synonymous	Exon 13 of 14	ENSP00000521702.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.12e-7 AC: 1 AN: 1404194 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 693176

African (AFR) AF: 0.00 AC: 0 AN: 31886

American (AMR) AF: 0.00 AC: 0 AN: 36782

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25174

East Asian (EAS) AF: 0.00 AC: 0 AN: 36260

South Asian (SAS) AF: 0.00 AC: 0 AN: 79600

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48636

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5540

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1082162

Other (OTH) AF: 0.0000172 AC: 1 AN: 58154

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.17
DANN	Benign	0.70
PhyloP100		-4.9

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2229136; hg19: chr10-45939617;