rs187523060

Variant names:

• chr10-45395902-C-T
• rs187523060
• NM_000698.5:c.397C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-45395902-C-T
• chr10-45395902-C-A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001320862.2(ALOX5):​c.-39C>T variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.000202 in 1,614,200 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 (★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00021 (2 hom.)
• Consequence: ALOX5 NM_001320862.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.39
• Publications: 7 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04325679).
• BP6: Variant 10-45395902-C-T is Benign according to our data. Variant chr10-45395902-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 741995.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 13 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001320862.2. 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.397C>T	p.Arg133Cys	missense	Exon 3 of 14	NP_000689.1	P09917-1
	ALOX5	NM_001320862.2		c.-39C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 14	NP_001307791.1
	ALOX5	NM_001320861.2		c.397C>T	p.Arg133Cys	missense	Exon 3 of 14	NP_001307790.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALOX5	ENST00000374391.7	TSL:1 MANE Select	c.397C>T	p.Arg133Cys	missense	Exon 3 of 14	ENSP00000363512.2	P09917-1
	ALOX5	ENST00000542434.5	TSL:1	c.397C>T	p.Arg133Cys	missense	Exon 3 of 13	ENSP00000437634.1	P09917-2
	ALOX5	ENST00000851643.1		c.397C>T	p.Arg133Cys	missense	Exon 3 of 14	ENSP00000521702.1

Frequencies

GnomAD3 genomes AF: 0.0000854 AC: 13 AN: 152200 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000485 AC: 122 AN: 251474 AF XY: 0.000625

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000214 AC: 313 AN: 1461882 Hom.: 2 Cov.: 31 AF XY: 0.000292 AC XY: 212 AN XY: 727244

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.000403 AC: 16 AN: 39700

South Asian (SAS) AF: 0.00303 AC: 261 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.0000171 AC: 19 AN: 1112002

Other (OTH) AF: 0.000232 AC: 14 AN: 60396

GnomAD4 genome AF: 0.0000853 AC: 13 AN: 152318 Hom.: 0 Cov.: 33 AF XY: 0.000134 AC XY: 10 AN XY: 74480

African (AFR) AF: 0.0000241 AC: 1 AN: 41570

American (AMR) AF: 0.00 AC: 0 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000966 AC: 5 AN: 5178

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000138 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.000568 AC: 69

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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	0.22
BayesDel_addAF	Benign	-0.083	T
BayesDel_noAF	Uncertain	0.11
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.79	D
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Uncertain	0.88	D
M_CAP	Benign	0.068	D
MetaRNN	Benign	0.043	T
MetaSVM	Uncertain	0.67	D
MutationAssessor	Uncertain	2.4	M
PhyloP100		4.4
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Uncertain	0.58
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.016	D
Polyphen		1.0	D
Vest4		0.66
MVP		0.96
MPC		0.59
ClinPred		0.11	T
GERP RS		6.0
Varity_R		0.52
gMVP		0.74
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs187523060; hg19: chr10-45891350; COSMIC: COSV65553112;