chr17-6999441-A-G

Variant names:

• chr17-6999441-A-G
• rs1126667
• NM_000697.3:c.782A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000697.3(ALOX12):​c.782A>G​(p.Gln261Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 1,612,702 control chromosomes in the GnomAD database, including 276,802 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 (★★).

• Frequency:
  • Genomes: 𝑓 0.61 (28848 hom., cov: 32)
  • Exomes 𝑓: 0.58 (247954 hom.)
• Consequence: ALOX12 NM_000697.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.59
• Publications: 78 publications found

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]

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

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=3.380869E-6).
• BP6: Variant 17-6999441-A-G is Benign according to our data. Variant chr17-6999441-A-G is described in ClinVar as Benign. ClinVar VariationId is 1224614.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.658 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.782A>G	p.Gln261Arg	missense	Exon 6 of 14	NP_000688.2	P18054
	ALOX12-AS1	NR_040089.1		n.233+10355T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALOX12	ENST00000251535.11	TSL:1 MANE Select	c.782A>G	p.Gln261Arg	missense	Exon 6 of 14	ENSP00000251535.6	P18054
	ALOX12	ENST00000915595.1		c.782A>G	p.Gln261Arg	missense	Exon 6 of 14	ENSP00000585654.1
	ALOX12	ENST00000480801.1	TSL:3	c.284A>G	p.Gln95Arg	missense	Exon 4 of 5	ENSP00000467033.1	K7ENN9

Frequencies

GnomAD3 genomes AF: 0.614 AC: 93234 AN: 151892 Hom.: 28809 Cov.: 32

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.597

Gnomad AMR AF: 0.669

Gnomad ASJ AF: 0.545

Gnomad EAS AF: 0.526

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.655

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.596

GnomAD2 exomes AF: 0.599 AC: 150620 AN: 251250 AF XY: 0.592

Gnomad AFR exome AF: 0.667

Gnomad AMR exome AF: 0.699

Gnomad ASJ exome AF: 0.549

Gnomad EAS exome AF: 0.510

Gnomad FIN exome AF: 0.670

Gnomad NFE exome AF: 0.580

Gnomad OTH exome AF: 0.586

GnomAD4 exome AF: 0.581 AC: 848652 AN: 1460692 Hom.: 247954 Cov.: 53 AF XY: 0.579 AC XY: 421119 AN XY: 726710

African (AFR) AF: 0.664 AC: 22200 AN: 33458

American (AMR) AF: 0.695 AC: 31057 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.546 AC: 14256 AN: 26130

East Asian (EAS) AF: 0.568 AC: 22551 AN: 39694

South Asian (SAS) AF: 0.547 AC: 47148 AN: 86232

European-Finnish (FIN) AF: 0.663 AC: 35419 AN: 53410

Middle Eastern (MID) AF: 0.574 AC: 3312 AN: 5768

European-Non Finnish (NFE) AF: 0.575 AC: 638293 AN: 1110940

Other (OTH) AF: 0.570 AC: 34416 AN: 60350

GnomAD4 genome AF: 0.614 AC: 93323 AN: 152010 Hom.: 28848 Cov.: 32 AF XY: 0.617 AC XY: 45842 AN XY: 74286

African (AFR) AF: 0.663 AC: 27491 AN: 41444

American (AMR) AF: 0.669 AC: 10226 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.545 AC: 1891 AN: 3472

East Asian (EAS) AF: 0.525 AC: 2706 AN: 5152

South Asian (SAS) AF: 0.540 AC: 2595 AN: 4808

European-Finnish (FIN) AF: 0.655 AC: 6933 AN: 10584

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.582 AC: 39515 AN: 67952

Other (OTH) AF: 0.595 AC: 1256 AN: 2110

Alfa AF: 0.590 Hom.: 121861

Bravo AF: 0.615

TwinsUK AF: 0.573 AC: 2123

ALSPAC AF: 0.575 AC: 2217

ESP6500AA AF: 0.667 AC: 2939

ESP6500EA AF: 0.578 AC: 4970

ExAC AF: 0.594 AC: 72163

Asia WGS AF: 0.543 AC: 1894 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.0030
DANN	Benign	0.80
DEOGEN2	Benign	0.23	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.48	T
MetaRNN	Benign	0.0000034	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		-1.6
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.19
Sift	Benign	0.23	T
Sift4G	Benign	0.71	T
Polyphen		0.0	B
Vest4		0.0070
MPC		0.30
ClinPred		0.011	T
GERP RS		-6.1
Varity_R		0.058
gMVP		0.18
Mutation Taster		=98/2	polymorphism (auto)

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: rs1126667; hg19: chr17-6902760; COSMIC: COSV52350211; COSMIC: COSV52350211;