chr17-6995799-C-T

Variant names:

• chr17-6995799-C-T
• rs9897850
• ENST00000399541.7:n.250-10259G>A

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.250-10259G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 152,072 control chromosomes in the GnomAD database, including 17,749 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.48 (17749 hom., cov: 33)
• Consequence: MIR497HG ENST00000399541.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.206
• Publications: 8 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 17-6995799-C-T is Benign according to our data. Variant chr17-6995799-C-T is described in ClinVar as Benign. ClinVar VariationId is 1269983.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX12-AS1	NR_040089.1	n.234-10259G>A		intron_variant	Intron 2 of 2
ALOX12	NM_000697.3	c.-319C>T		upstream_gene_variant		ENST00000251535.11	NP_000688.2
ALOX12	XM_011523780.3	c.-319C>T		upstream_gene_variant			XP_011522082.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX12	ENST00000251535.11	c.-319C>T		upstream_gene_variant		1	NM_000697.3	ENSP00000251535.6

Frequencies

GnomAD3 genomes AF: 0.481 AC: 73083 AN: 151954 Hom.: 17730 Cov.: 33

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.491

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.506

Gnomad OTH AF: 0.484

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

GnomAD4 genome AF: 0.481 AC: 73142 AN: 152072 Hom.: 17749 Cov.: 33 AF XY: 0.479 AC XY: 35631 AN XY: 74328

African (AFR) AF: 0.475 AC: 19725 AN: 41504

American (AMR) AF: 0.396 AC: 6049 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.478 AC: 1656 AN: 3468

East Asian (EAS) AF: 0.396 AC: 2036 AN: 5146

South Asian (SAS) AF: 0.492 AC: 2373 AN: 4824

European-Finnish (FIN) AF: 0.501 AC: 5300 AN: 10584

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.506 AC: 34406 AN: 67940

Other (OTH) AF: 0.483 AC: 1021 AN: 2112

Alfa AF: 0.491 Hom.: 2439

Bravo AF: 0.466

Asia WGS AF: 0.435 AC: 1519 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.7
DANN	Benign	0.77
PhyloP100		0.21
PromoterAI		0.040	Neutral
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: rs9897850; hg19: chr17-6899118;