17-6997043-C-T

Variant names:

• chr17-6997043-C-T
• rs2070589
• NM_000697.3:c.337+16C>T

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.337+16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 1,522,744 control chromosomes in the GnomAD database, including 260,078 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.61 (28859 hom., cov: 33)
  • Exomes 𝑓: 0.58 (231219 hom.)
• Consequence: ALOX12 NM_000697.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.35
• Publications: 10 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 (BayesDel_noAF=-0.79).
• BP6: Variant 17-6997043-C-T is Benign according to our data. Variant chr17-6997043-C-T is described in ClinVar as Benign. ClinVar VariationId is 1289083.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.657 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.337+16C>T		intron	N/A	NP_000688.2	P18054
	ALOX12-AS1	NR_040089.1		n.234-11503G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALOX12	ENST00000251535.11	TSL:1 MANE Select	c.337+16C>T		intron	N/A	ENSP00000251535.6	P18054
	ALOX12	ENST00000915595.1		c.337+16C>T		intron	N/A	ENSP00000585654.1
	ALOX12	ENST00000480801.1	TSL:3	c.46+16C>T		intron	N/A	ENSP00000467033.1	K7ENN9

Frequencies

GnomAD3 genomes AF: 0.614 AC: 93277 AN: 151994 Hom.: 28822 Cov.: 33

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.668

Gnomad ASJ AF: 0.542

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.658

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.594

GnomAD2 exomes AF: 0.600 AC: 84535 AN: 140788 AF XY: 0.590

Gnomad AFR exome AF: 0.678

Gnomad AMR exome AF: 0.694

Gnomad ASJ exome AF: 0.549

Gnomad EAS exome AF: 0.511

Gnomad FIN exome AF: 0.675

Gnomad NFE exome AF: 0.583

Gnomad OTH exome AF: 0.586

GnomAD4 exome AF: 0.579 AC: 794111 AN: 1370632 Hom.: 231219 Cov.: 58 AF XY: 0.578 AC XY: 388632 AN XY: 672192

African (AFR) AF: 0.665 AC: 20804 AN: 31284

American (AMR) AF: 0.690 AC: 24197 AN: 35072

Ashkenazi Jewish (ASJ) AF: 0.542 AC: 13345 AN: 24634

East Asian (EAS) AF: 0.572 AC: 20132 AN: 35212

South Asian (SAS) AF: 0.546 AC: 42743 AN: 78290

European-Finnish (FIN) AF: 0.661 AC: 26731 AN: 40454

Middle Eastern (MID) AF: 0.565 AC: 2608 AN: 4614

European-Non Finnish (NFE) AF: 0.574 AC: 611197 AN: 1064192

Other (OTH) AF: 0.569 AC: 32354 AN: 56880

GnomAD4 genome AF: 0.614 AC: 93363 AN: 152112 Hom.: 28859 Cov.: 33 AF XY: 0.617 AC XY: 45881 AN XY: 74366

African (AFR) AF: 0.663 AC: 27502 AN: 41464

American (AMR) AF: 0.668 AC: 10217 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.542 AC: 1879 AN: 3468

East Asian (EAS) AF: 0.521 AC: 2690 AN: 5160

South Asian (SAS) AF: 0.538 AC: 2594 AN: 4826

European-Finnish (FIN) AF: 0.658 AC: 6977 AN: 10600

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.582 AC: 39537 AN: 67988

Other (OTH) AF: 0.594 AC: 1254 AN: 2112

Alfa AF: 0.594 Hom.: 8764

Bravo AF: 0.615

Asia WGS AF: 0.541 AC: 1885 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
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.58
DANN	Benign	0.86
PhyloP100		-1.4
PromoterAI		0.010	Neutral
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: rs2070589; hg19: chr17-6900362; COSMIC: COSV52349098; COSMIC: COSV52349098;