rs312466

Variant names:

• chr17-6995902-G-A
• rs312466
• ENST00000399541.7:n.250-10362C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-6995902-G-A
• chr17-6995902-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000399541.7(MIR497HG):​n.250-10362C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 152,158 control chromosomes in the GnomAD database, including 9,632 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.34 (9632 hom., cov: 34)
• Consequence: MIR497HG ENST00000399541.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.773
• Publications: 20 publications found

Genes affected

MIR497HG (HGNC:39523): (mir-497-195 cluster host gene)

ALOX12-AS1 (HGNC:51342): (ALOX12 antisense RNA 1)

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]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 17-6995902-G-A is Benign according to our data. Variant chr17-6995902-G-A is described in ClinVar as Benign. ClinVar VariationId is 1178415.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000399541.7. 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-AS1	NR_040089.1		n.234-10362C>T		intron	N/A
	ALOX12	NM_000697.3	MANE Select	c.-216G>A		upstream_gene	N/A	NP_000688.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR497HG	ENST00000399541.7	TSL:2	n.250-10362C>T		intron	N/A
	MIR497HG	ENST00000570562.5	TSL:3	n.237+13894C>T		intron	N/A
	MIR497HG	ENST00000572385.6	TSL:4	n.233+13894C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51616 AN: 152040 Hom.: 9624 Cov.: 34

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.367

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.339 AC: 51626 AN: 152158 Hom.: 9632 Cov.: 34 AF XY: 0.337 AC XY: 25113 AN XY: 74410

African (AFR) AF: 0.193 AC: 8008 AN: 41532

American (AMR) AF: 0.269 AC: 4117 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 1592 AN: 3472

East Asian (EAS) AF: 0.474 AC: 2446 AN: 5158

South Asian (SAS) AF: 0.456 AC: 2203 AN: 4828

European-Finnish (FIN) AF: 0.341 AC: 3615 AN: 10600

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.418 AC: 28379 AN: 67968

Other (OTH) AF: 0.368 AC: 778 AN: 2112

Alfa AF: 0.385 Hom.: 13366

Bravo AF: 0.327

Asia WGS AF: 0.426 AC: 1478 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	-0.78
CADD	Benign	7.8
DANN	Benign	0.96
PhyloP100		0.77
PromoterAI		0.60	Over-expression
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs312466; hg19: chr17-6899221; COSMIC: COSV52352886;