17-7000625-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000697.3(ALOX12):​c.951+146G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000013 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ALOX12 NM_000697.3 intron
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

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>C		intron	N/A	NP_000688.2
	ALOX12-AS1	NR_040089.1		n.233+9171C>G		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>C		intron	N/A	ENSP00000251535.6
	ALOX12	ENST00000915595.1		c.951+146G>C		intron	N/A	ENSP00000585654.1
	MIR497HG	ENST00000399541.7	TSL:2	n.249+9171C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000133 AC: 1 AN: 753342 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 382178

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 18268

American (AMR) AF: 0.00 AC: 0 AN: 20950

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15468

East Asian (EAS) AF: 0.00 AC: 0 AN: 33078

South Asian (SAS) AF: 0.00 AC: 0 AN: 52688

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36888

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2538

European-Non Finnish (NFE) AF: 0.00000186 AC: 1 AN: 537710

Other (OTH) AF: 0.00 AC: 0 AN: 35754

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 27875

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
DANN	Benign	0.57
PhyloP100		-0.37

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;