chr17-7001615-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000697.3(ALOX12):c.965A>G(p.Asn322Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 1,612,400 control chromosomes in the GnomAD database, including 136,170 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N322I) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.34 ( 9626 hom., cov: 32)

Exomes 𝑓: 0.41 ( 126544 hom. )

Consequence

ALOX12
NM_000697.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0450

Publications

64 publications found

Variant links:

Genes affected

ALOX12 (HGNC:429): (arachidonate 12-lipoxygenase, 12S type) This gene encodes a member of the lipoxygenase family of proteins. The encoded enzyme acts on different polyunsaturated fatty acid substrates to generate bioactive lipid mediators including eicosanoids and lipoxins. The encoded enzyme and its reaction products have been shown to regulate platelet function. Elevated expression of this gene has been observed in pancreatic islets derived from human diabetes patients. Allelic variants in this gene may be associated with susceptibility to toxoplasmosis. Multiple pseudogenes of this gene have been identified in the human genome. [provided by RefSeq, Aug 2017]

ALOX12 links:

MIR497HG (HGNC:39523): (mir-497-195 cluster host gene)

MIR497HG links:

ALOX12-AS1 (HGNC:51342): (ALOX12 antisense RNA 1)

ALOX12-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.2104383E-4).

BP6

Variant 17-7001615-A-G is Benign according to our data. Variant chr17-7001615-A-G is described in ClinVar as Benign. ClinVar VariationId is 1233269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000697.3. 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
	ALOX12	NM_000697.3	MANE Select	c.965A>G	p.Asn322Ser	missense	Exon 8 of 14	NP_000688.2	P18054
	ALOX12-AS1	NR_040089.1		n.233+8181T>C		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ALOX12	ENST00000251535.11	TSL:1 MANE Select	c.965A>G	p.Asn322Ser	missense	Exon 8 of 14	ENSP00000251535.6	P18054
ALOX12	ENST00000915595.1		c.965A>G	p.Asn322Ser	missense	Exon 8 of 14	ENSP00000585654.1
MIR497HG	ENST00000399540.3	TSL:2	n.1254T>C		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.340

AC:

51617

AN:

151772

Hom.:

9622

Cov.:

show subpopulations

Gnomad AFR

AF:

0.194

Gnomad AMI

AF:

0.399

Gnomad AMR

AF:

0.270

Gnomad ASJ

AF:

0.455

Gnomad EAS

AF:

0.466

Gnomad SAS

AF:

0.454

Gnomad FIN

AF:

0.344

Gnomad MID

AF:

0.427

Gnomad NFE

AF:

0.418

Gnomad OTH

AF:

0.365

GnomAD2 exomes

AF:

0.379

AC:

95286

AN:

251198

AF XY:

0.392

show subpopulations

Gnomad AFR exome

AF:

0.187

Gnomad AMR exome

AF:

0.231

Gnomad ASJ exome

AF:

0.451

Gnomad EAS exome

AF:

0.483

Gnomad FIN exome

AF:

0.330

Gnomad NFE exome

AF:

0.419

Gnomad OTH exome

AF:

0.397

GnomAD4 exome

AF:

0.412

AC:

601532

AN:

1460510

Hom.:

126544

Cov.:

AF XY:

0.414

AC XY:

300988

AN XY:

726632

show subpopulations

African (AFR)

AF:

0.190

AC:

6351

AN:

33470

American (AMR)

AF:

0.235

AC:

10494

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.454

AC:

11867

AN:

26122

East Asian (EAS)

AF:

0.425

AC:

16882

AN:

39690

South Asian (SAS)

AF:

0.446

AC:

38494

AN:

86216

European-Finnish (FIN)

AF:

0.336

AC:

17967

AN:

53412

Middle Eastern (MID)

AF:

0.414

AC:

2385

AN:

5764

European-Non Finnish (NFE)

AF:

0.425

AC:

472034

AN:

1110772

Other (OTH)

AF:

0.415

AC:

25058

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

15987

31975

47962

63950

79937

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14416

28832

43248

57664

72080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.340

AC:

51624

AN:

151890

Hom.:

9626

Cov.:

AF XY:

0.338

AC XY:

25093

AN XY:

74240

show subpopulations

African (AFR)

AF:

0.194

AC:

8037

AN:

41402

American (AMR)

AF:

0.270

AC:

4112

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.455

AC:

1579

AN:

3470

East Asian (EAS)

AF:

0.466

AC:

2407

AN:

5162

South Asian (SAS)

AF:

0.454

AC:

2189

AN:

4818

European-Finnish (FIN)

AF:

0.344

AC:

3622

AN:

10542

Middle Eastern (MID)

AF:

0.418

AC:

122

AN:

292

European-Non Finnish (NFE)

AF:

0.418

AC:

28421

AN:

67928

Other (OTH)

AF:

0.366

AC:

773

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1692

3384

5077

6769

8461

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

520

1040

1560

2080

2600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.392

Hom.:

37128

Bravo

AF:

0.327

TwinsUK

AF:

0.426

AC:

1578

ALSPAC

AF:

0.421

AC:

1622

ESP6500AA

AF:

0.196

AC:

862

ESP6500EA

AF:

0.422

AC:

3626

ExAC

AF:

0.384

AC:

46658

Asia WGS

AF:

0.426

AC:

1478

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.60

CADD

Benign

2.5

(source)

DANN

Benign

0.67

DEOGEN2

Benign

0.15

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.068

LIST_S2

Benign

0.28

MetaRNN

Benign

0.00022

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.17

PhyloP100

-0.045

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.34

REVEL

Benign

0.13

Sift

Benign

0.62

Sift4G

Benign

0.59

Polyphen

0.0

Vest4

0.014

MPC

0.22

ClinPred

0.00053

GERP RS

-4.4

Varity_R

0.20

gMVP

0.069

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over