17-6998520-G-C

Variant names:

• chr17-6998520-G-C
• rs145526271
• NM_000697.3:c.349G>C

Variant summary

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

The NM_000697.3(ALOX12):​c.349G>C​(p.Gly117Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000273 in 1,613,590 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0012 (1 hom., cov: 31)
  • Exomes 𝑓: 0.00018 (2 hom.)
• Consequence: ALOX12 NM_000697.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.24
• Publications: 2 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00692302).
• BP6: Variant 17-6998520-G-C is Benign according to our data. Variant chr17-6998520-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2647316.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

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.349G>C	p.Gly117Arg	missense	Exon 3 of 14	NP_000688.2	P18054
	ALOX12-AS1	NR_040089.1		n.233+11276C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALOX12	ENST00000251535.11	TSL:1 MANE Select	c.349G>C	p.Gly117Arg	missense	Exon 3 of 14	ENSP00000251535.6	P18054
	ALOX12	ENST00000915595.1		c.349G>C	p.Gly117Arg	missense	Exon 3 of 14	ENSP00000585654.1
	ALOX12	ENST00000480801.1	TSL:3	c.58G>C	p.Gly20Arg	missense	Exon 2 of 5	ENSP00000467033.1	K7ENN9

Frequencies

GnomAD3 genomes AF: 0.00118 AC: 179 AN: 152188 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.00379

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000524

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000399 AC: 100 AN: 250528 AF XY: 0.000347

Gnomad AFR exome AF: 0.00385

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00278

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000618

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000177 AC: 259 AN: 1461284 Hom.: 2 Cov.: 31 AF XY: 0.000155 AC XY: 113 AN XY: 726870

African (AFR) AF: 0.00394 AC: 132 AN: 33466

American (AMR) AF: 0.0000895 AC: 4 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00234 AC: 61 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86096

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00173 AC: 10 AN: 5768

European-Non Finnish (NFE) AF: 0.0000207 AC: 23 AN: 1111660

Other (OTH) AF: 0.000480 AC: 29 AN: 60384

GnomAD4 genome AF: 0.00119 AC: 181 AN: 152306 Hom.: 1 Cov.: 31 AF XY: 0.00101 AC XY: 75 AN XY: 74478

African (AFR) AF: 0.00383 AC: 159 AN: 41558

American (AMR) AF: 0.000523 AC: 8 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00230 AC: 8 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68020

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.000345 Hom.: 0

Bravo AF: 0.00137

ESP6500AA AF: 0.00295 AC: 13

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000436 AC: 53

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000178

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	0.086
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	21
DANN	Benign	0.91
DEOGEN2	Benign	0.096	T
Eigen	Benign	-0.22
Eigen_PC	Benign	0.010
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.0069	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.8	L
PhyloP100		2.2
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.15	N
REVEL	Benign	0.056
Sift	Benign	0.57	T
Sift4G	Benign	0.67	T
Polyphen		0.0010	B
Vest4		0.42
MutPred		0.41		Gain of catalytic residue at G117 (P = 0.0879)
MVP		0.47
MPC		0.33
ClinPred		0.0086	T
GERP RS		4.5
Varity_R		0.11
gMVP		0.62
Mutation Taster		=94/6	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: rs145526271; hg19: chr17-6901839;