13-91350551-A-G

Position:

• chr13-91350551-A-G

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NR_027350.1(MIR17HG):​n.994A>G 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 0.00176 in 532,734 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0019 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0017 (2 hom.)
• Consequence: MIR17HG NR_027350.1 non_coding_transcript_exon
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.349

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]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 13-91350551-A-G is Benign according to our data. Variant chr13-91350551-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3050195.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd4 at 283 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIR17HG	NR_027350.1	n.994A>G		non_coding_transcript_exon_variant	2/2
MIR17HG	NR_027349.1	n.284+325A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIR17HG	ENST00000710422.1	n.407+325A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00186 AC: 283 AN: 152258 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000506

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.000785

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000413

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00338

Gnomad OTH AF: 0.00143

GnomAD4 exome AF: 0.00173 AC: 657 AN: 380358 Hom.: 2 Cov.: 0 AF XY: 0.00151 AC XY: 327 AN XY: 216662

Gnomad4 AFR exome AF: 0.000479

Gnomad4 AMR exome AF: 0.000662

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000180

Gnomad4 FIN exome AF: 0.000186

Gnomad4 NFE exome AF: 0.00297

Gnomad4 OTH exome AF: 0.00241

GnomAD4 genome AF: 0.00186 AC: 283 AN: 152376 Hom.: 1 Cov.: 33 AF XY: 0.00165 AC XY: 123 AN XY: 74518

Gnomad4 AFR AF: 0.000505

Gnomad4 AMR AF: 0.000784

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.00338

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00285 Hom.: 0

Bravo AF: 0.00187

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

MIR17HG-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 21, 2021

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	16
DANN	Benign	0.80
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.1

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs373341333; hg19: chr13-92002805;