rs11078659

Variant names:

• chr17-7000625-G-A
• rs11078659
• NM_000697.3:c.951+146G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-7000625-G-A
• chr17-7000625-G-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000697.3(ALOX12):​c.951+146G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 903,006 control chromosomes in the GnomAD database, including 109,812 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.48 (17736 hom., cov: 32)
  • Exomes 𝑓: 0.49 (92076 hom.)
• Consequence: ALOX12 NM_000697.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.370
• Publications: 5 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 17-7000625-G-A is Benign according to our data. Variant chr17-7000625-G-A is described in ClinVar as Benign. ClinVar VariationId is 1179701.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.505 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALOX12	NM_000697.3	MANE Select	c.951+146G>A		intron	N/A	NP_000688.2
	ALOX12-AS1	NR_040089.1		n.233+9171C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALOX12	ENST00000251535.11	TSL:1 MANE Select	c.951+146G>A		intron	N/A	ENSP00000251535.6
	ALOX12	ENST00000915595.1		c.951+146G>A		intron	N/A	ENSP00000585654.1
	MIR497HG	ENST00000399541.7	TSL:2	n.249+9171C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73087 AN: 151752 Hom.: 17722 Cov.: 32

Gnomad AFR AF: 0.469

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.497

Gnomad FIN AF: 0.505

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.509

Gnomad OTH AF: 0.484

GnomAD4 exome AF: 0.489 AC: 367265 AN: 751136 Hom.: 92076 AF XY: 0.490 AC XY: 186770 AN XY: 381062

African (AFR) AF: 0.456 AC: 8319 AN: 18230

American (AMR) AF: 0.317 AC: 6620 AN: 20888

Ashkenazi Jewish (ASJ) AF: 0.479 AC: 7389 AN: 15432

East Asian (EAS) AF: 0.460 AC: 15206 AN: 33042

South Asian (SAS) AF: 0.505 AC: 26526 AN: 52566

European-Finnish (FIN) AF: 0.519 AC: 19098 AN: 36804

Middle Eastern (MID) AF: 0.532 AC: 1348 AN: 2536

European-Non Finnish (NFE) AF: 0.496 AC: 265689 AN: 535966

Other (OTH) AF: 0.479 AC: 17070 AN: 35672

GnomAD4 genome AF: 0.482 AC: 73143 AN: 151870 Hom.: 17736 Cov.: 32 AF XY: 0.480 AC XY: 35637 AN XY: 74178

African (AFR) AF: 0.469 AC: 19408 AN: 41388

American (AMR) AF: 0.395 AC: 6026 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 1661 AN: 3472

East Asian (EAS) AF: 0.411 AC: 2117 AN: 5154

South Asian (SAS) AF: 0.497 AC: 2392 AN: 4810

European-Finnish (FIN) AF: 0.505 AC: 5319 AN: 10526

Middle Eastern (MID) AF: 0.527 AC: 154 AN: 292

European-Non Finnish (NFE) AF: 0.509 AC: 34622 AN: 67962

Other (OTH) AF: 0.484 AC: 1018 AN: 2104

Alfa AF: 0.498 Hom.: 27875

Bravo AF: 0.466

Asia WGS AF: 0.442 AC: 1542 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: 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
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.2
DANN	Benign	0.57
PhyloP100		-0.37
Mutation Taster		=100/0	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: rs11078659; hg19: chr17-6903944; COSMIC: COSV52351729; COSMIC: COSV52351729;