ENST00000581816.2:n.3332C>A

Variant names:

• chr13-91353141-C-A
• rs1875410050
• ENST00000581816.2:n.3332C>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP6

The ENST00000581816.2(MIR17HG):​n.3332C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00041 (0 hom., cov: 29)
  • Failed GnomAD Quality Control
• Consequence: MIR17HG ENST00000581816.2 non_coding_transcript_exon
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.654
• Publications: 0 publications found

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]

MIR17HG Gene-Disease associations (from GenCC):

• Feingold syndrome type 2

  Inheritance: AD, Unknown Classification: STRONG, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ENSG00000292285 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 13-91353141-C-A is Benign according to our data. Variant chr13-91353141-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3032970.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000581816.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR17HG	NR_197388.1	MANE Select	n.3332C>A		non_coding_transcript_exon	Exon 3 of 3
	MIR17HG	NR_027350.2		n.3717C>A		non_coding_transcript_exon	Exon 2 of 2
	MIR17HG	NR_027349.2		n.418-792C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR17HG	ENST00000581816.2	TSL:1 MANE Select	n.3332C>A		non_coding_transcript_exon	Exon 3 of 3
	MIR17HG	ENST00000582141.7	TSL:1	n.3717C>A		non_coding_transcript_exon	Exon 2 of 2
	MIR17HG	ENST00000400282.8	TSL:1	n.285-792C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000405 AC: 53 AN: 130888 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.000366

Gnomad AMI AF: 0.00120

Gnomad AMR AF: 0.000474

Gnomad ASJ AF: 0.000310

Gnomad EAS AF: 0.00143

Gnomad SAS AF: 0.00130

Gnomad FIN AF: 0.000613

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000274

Gnomad OTH AF: 0.00

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

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000412 AC: 54 AN: 130924 Hom.: 0 Cov.: 29 AF XY: 0.000478 AC XY: 30 AN XY: 62778

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000366 AC: 13 AN: 35524

American (AMR) AF: 0.000552 AC: 7 AN: 12692

Ashkenazi Jewish (ASJ) AF: 0.000310 AC: 1 AN: 3224

East Asian (EAS) AF: 0.00143 AC: 6 AN: 4196

South Asian (SAS) AF: 0.00130 AC: 5 AN: 3848

European-Finnish (FIN) AF: 0.000613 AC: 4 AN: 6528

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 226

European-Non Finnish (NFE) AF: 0.000274 AC: 17 AN: 62066

Other (OTH) AF: 0.00 AC: 0 AN: 1790

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	MIR17HG-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.63
DANN	Benign	0.18
PhyloP100		-0.65
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs1875410050; hg19: chr13-92005395;