chr17-6999441-A-G

Position:

• chr17-6999441-A-G

Variant summary

Our verdict is Benign. Variant got -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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALOX12	NM_000697.3	c.782A>G	p.Gln261Arg	missense_variant	6/14	ENST00000251535.11
ALOX12-AS1	NR_040089.1	n.233+10355T>C		intron_variant, non_coding_transcript_variant
ALOX12	XM_011523780.3	c.575A>G	p.Gln192Arg	missense_variant	5/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALOX12	ENST00000251535.11	c.782A>G	p.Gln261Arg	missense_variant	6/14	1	NM_000697.3	P1
ALOX12-AS1	ENST00000653385.1	n.139+12755T>C		intron_variant, non_coding_transcript_variant

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

GnomAD3 exomes AF: 0.599 AC: 150620 AN: 251250 Hom.: 45707 AF XY: 0.592 AC XY: 80363 AN XY: 135774

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 SAS exome AF: 0.546

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

Gnomad4 AFR exome AF: 0.664

Gnomad4 AMR exome AF: 0.695

Gnomad4 ASJ exome AF: 0.546

Gnomad4 EAS exome AF: 0.568

Gnomad4 SAS exome AF: 0.547

Gnomad4 FIN exome AF: 0.663

Gnomad4 NFE exome AF: 0.575

Gnomad4 OTH exome AF: 0.570

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

Gnomad4 AFR AF: 0.663

Gnomad4 AMR AF: 0.669

Gnomad4 ASJ AF: 0.545

Gnomad4 EAS AF: 0.525

Gnomad4 SAS AF: 0.540

Gnomad4 FIN AF: 0.655

Gnomad4 NFE AF: 0.582

Gnomad4 OTH AF: 0.595

Alfa AF: 0.582 Hom.: 61980

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

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	This variant is associated with the following publications: (PMID: 20626912, 21104233, 24282679, 16514435, 17460548, 19885615, 22864639, 22977504, 18640486) -

Computational scores

Source: dbNSFP v4.3

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;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.48	T;T
MetaRNN	Benign	0.0000034	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L;.
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-1.1	N;.
REVEL	Benign	0.19
Sift	Benign	0.23	T;.
Sift4G	Benign	0.71	T;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

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

Publications

LitVar

Other links and lift over

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