17-7001742-T-G

Variant names:

• chr17-7001742-T-G
• rs1042357
• NM_000697.3:c.1092T>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000697.3(ALOX12):​c.1092T>G​(p.Thr364Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 1,613,744 control chromosomes in the GnomAD database, including 271,121 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.59 (26225 hom., cov: 31)
  • Exomes 𝑓: 0.58 (244896 hom.)
• Consequence: ALOX12 NM_000697.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.75
• Publications: 38 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 17-7001742-T-G is Benign according to our data. Variant chr17-7001742-T-G is described in ClinVar as Benign. ClinVar VariationId is 1247877.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.75 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.644 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.1092T>G	p.Thr364Thr	synonymous	Exon 8 of 14	NP_000688.2
	ALOX12-AS1	NR_040089.1		n.233+8054A>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.1092T>G	p.Thr364Thr	synonymous	Exon 8 of 14	ENSP00000251535.6
	ALOX12	ENST00000915595.1		c.1092T>G	p.Thr364Thr	synonymous	Exon 8 of 14	ENSP00000585654.1
	MIR497HG	ENST00000399540.3	TSL:2	n.1127A>C		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.585 AC: 88894 AN: 151862 Hom.: 26193 Cov.: 31

Gnomad AFR AF: 0.566

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.527

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.581

Gnomad OTH AF: 0.579

GnomAD2 exomes AF: 0.592 AC: 148784 AN: 251418 AF XY: 0.586

Gnomad AFR exome AF: 0.568

Gnomad AMR exome AF: 0.694

Gnomad ASJ exome AF: 0.536

Gnomad EAS exome AF: 0.511

Gnomad FIN exome AF: 0.670

Gnomad NFE exome AF: 0.580

Gnomad OTH exome AF: 0.581

GnomAD4 exome AF: 0.578 AC: 844203 AN: 1461764 Hom.: 244896 Cov.: 58 AF XY: 0.576 AC XY: 419157 AN XY: 727194

African (AFR) AF: 0.557 AC: 18656 AN: 33478

American (AMR) AF: 0.689 AC: 30819 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 13921 AN: 26136

East Asian (EAS) AF: 0.570 AC: 22610 AN: 39698

South Asian (SAS) AF: 0.547 AC: 47179 AN: 86252

European-Finnish (FIN) AF: 0.664 AC: 35443 AN: 53416

Middle Eastern (MID) AF: 0.564 AC: 3254 AN: 5768

European-Non Finnish (NFE) AF: 0.574 AC: 638369 AN: 1111900

Other (OTH) AF: 0.562 AC: 33952 AN: 60392

GnomAD4 genome AF: 0.585 AC: 88975 AN: 151980 Hom.: 26225 Cov.: 31 AF XY: 0.590 AC XY: 43798 AN XY: 74290

African (AFR) AF: 0.567 AC: 23479 AN: 41434

American (AMR) AF: 0.655 AC: 9992 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1842 AN: 3470

East Asian (EAS) AF: 0.527 AC: 2715 AN: 5150

South Asian (SAS) AF: 0.540 AC: 2600 AN: 4812

European-Finnish (FIN) AF: 0.657 AC: 6941 AN: 10562

Middle Eastern (MID) AF: 0.565 AC: 165 AN: 292

European-Non Finnish (NFE) AF: 0.581 AC: 39476 AN: 67978

Other (OTH) AF: 0.579 AC: 1218 AN: 2104

Alfa AF: 0.579 Hom.: 38831

Bravo AF: 0.583

Asia WGS AF: 0.533 AC: 1857 AN: 3478

ClinVar

ClinVar submissions as Germline

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
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.52
DANN	Benign	0.30
PhyloP100		-1.8
Mutation Taster		=92/8	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1042357; hg19: chr17-6905061; COSMIC: COSV52349144; COSMIC: COSV52349144;