rs9589207

chr13-91351335-G-Achr13-91351335-G-C

Variant summary

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

The NR_027350.1(MIR17HG):n.1778G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00802 in 531,700 control chromosomes in the GnomAD database, including 156 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 0.021 (131 hom., cov: 33)
  • Exomes 𝑓: 0.0028 (25 hom.)
• Consequence: MIR17HG NR_027350.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.285

Genes affected

MIR17HG (HGNC:23564): (miR-17-92a-1 cluster host gene) This gene is the host gene for the MIR17-92 cluster, a group of at least six microRNAs (miRNAs) that may be involved in cell survival, proliferation, differentiation, and angiogenesis. Amplification of this gene has been found in several lymphomas and solid tumors. Two non-protein coding transcript variants have been found for this host gene, but only the longest is a polycistronic transcript containing the MIR17-92 cluster. [provided by RefSeq, May 2012]

MIR92A1 (HGNC:31643): (microRNA 92a-1) 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=-0.53).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.07 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MIR17HG	NR_027350.1	n.1778G>A		non_coding_transcript_exon_variant	2/2
MIR92A1	NR_029508.1	n.22G>A		non_coding_transcript_exon_variant	1/1
MIR17HG	NR_027349.1	n.284+1109G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIR92A1	ENST00000385233.3	n.22G>A		mature_miRNA_variant	1/1
MIR17HG	ENST00000710422.1	n.407+1109G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0210 AC: 3198 AN: 152162 Hom.: 130 Cov.: 33

Gnomad AFR AF: 0.0721

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.0158

GnomAD3 exomes AF: 0.00544 AC: 1367 AN: 251074 Hom.: 41 AF XY: 0.00375 AC XY: 510 AN XY: 135910

Gnomad AFR exome AF: 0.0734

Gnomad AMR exome AF: 0.00350

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000229

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000291

Gnomad OTH exome AF: 0.00277

GnomAD4 exome AF: 0.00278 AC: 1053 AN: 379420 Hom.: 25 Cov.: 0 AF XY: 0.00210 AC XY: 453 AN XY: 215446

Gnomad4 AFR exome AF: 0.0732

Gnomad4 AMR exome AF: 0.00356

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000375

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000195

Gnomad4 OTH exome AF: 0.00519

GnomAD4 genome AF: 0.0211 AC: 3209 AN: 152280 Hom.: 131 Cov.: 33 AF XY: 0.0200 AC XY: 1487 AN XY: 74474

Gnomad4 AFR AF: 0.0721

Gnomad4 AMR AF: 0.0105

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000265

Gnomad4 OTH AF: 0.0156

Alfa AF: 0.00583 Hom.: 47

Bravo AF: 0.0235

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
Cadd	Benign	11
Dann	Benign	0.87
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9589207; hg19: chr13-92003589;