rs10865292

Positions:

• chr2-55988917-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_126406.1(MIR217HG):​n.208+24692C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.91 in 481,352 control chromosomes in the GnomAD database, including 199,721 homozygotes. 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: 𝑓 0.92 (64440 hom., cov: 32)
  • Exomes 𝑓: 0.91 (135281 hom.)
• Consequence: MIR217HG NR_126406.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.205

Genes affected

MIR217HG (HGNC:50537): (MIR217 host gene)

(HGNC:):

MIR216A (HGNC:31593): (microRNA 216a) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MIR217HG	NR_126406.1	n.208+24692C>T		intron_variant, non_coding_transcript_variant
LOC105374690	XR_940109.3	n.587+36678G>A		intron_variant, non_coding_transcript_variant
MIR216A	NR_029629.1			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIR217HG	ENST00000446139.1	n.208+24692C>T		intron_variant, non_coding_transcript_variant		5
	ENST00000606639.1	n.82+36678G>A		intron_variant, non_coding_transcript_variant		1
MIR217HG	ENST00000701602.1	n.407+4956C>T		intron_variant, non_coding_transcript_variant
MIR216A	ENST00000385063.1			downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.919 AC: 139890 AN: 152148 Hom.: 64384 Cov.: 32

Gnomad AFR AF: 0.957

Gnomad AMI AF: 0.927

Gnomad AMR AF: 0.908

Gnomad ASJ AF: 0.877

Gnomad EAS AF: 0.879

Gnomad SAS AF: 0.909

Gnomad FIN AF: 0.885

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.911

Gnomad OTH AF: 0.900

GnomAD3 exomes AF: 0.907 AC: 220509 AN: 243126 Hom.: 100075 AF XY: 0.905 AC XY: 119051 AN XY: 131536

Gnomad AFR exome AF: 0.958

Gnomad AMR exome AF: 0.914

Gnomad ASJ exome AF: 0.881

Gnomad EAS exome AF: 0.872

Gnomad SAS exome AF: 0.906

Gnomad FIN exome AF: 0.879

Gnomad NFE exome AF: 0.911

Gnomad OTH exome AF: 0.909

GnomAD4 exome AF: 0.906 AC: 298269 AN: 329088 Hom.: 135281 Cov.: 0 AF XY: 0.905 AC XY: 166336 AN XY: 183700

Gnomad4 AFR exome AF: 0.955

Gnomad4 AMR exome AF: 0.913

Gnomad4 ASJ exome AF: 0.882

Gnomad4 EAS exome AF: 0.869

Gnomad4 SAS exome AF: 0.907

Gnomad4 FIN exome AF: 0.879

Gnomad4 NFE exome AF: 0.912

Gnomad4 OTH exome AF: 0.905

GnomAD4 genome AF: 0.919 AC: 140002 AN: 152264 Hom.: 64440 Cov.: 32 AF XY: 0.917 AC XY: 68232 AN XY: 74446

Gnomad4 AFR AF: 0.957

Gnomad4 AMR AF: 0.909

Gnomad4 ASJ AF: 0.877

Gnomad4 EAS AF: 0.879

Gnomad4 SAS AF: 0.909

Gnomad4 FIN AF: 0.885

Gnomad4 NFE AF: 0.911

Gnomad4 OTH AF: 0.896

Alfa AF: 0.910 Hom.: 11969

Bravo AF: 0.922

Asia WGS AF: 0.906 AC: 3150 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.71
DANN	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10865292; hg19: chr2-56216052;