chr13-91351555-C-T

Variant names:

• chr13-91351555-C-T
• rs139418718
• ENST00000581816.2:n.1746C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The ENST00000581816.2(MIR17HG):​n.1746C>T 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 0.000138 in 327,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00016 (0 hom.)
• Consequence: MIR17HG ENST00000581816.2 non_coding_transcript_exon
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.742
• 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]

ENSG00000292285 (HGNC:):

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

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 13-91351555-C-T is Benign according to our data. Variant chr13-91351555-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3059111.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd4 at 17 AD,Unknown gene.

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.1746C>T		non_coding_transcript_exon	Exon 3 of 3
	MIR17HG	NR_027350.2		n.2131C>T		non_coding_transcript_exon	Exon 2 of 2
	MIR17HG	NR_027349.2		n.417+1329C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR17HG	ENST00000581816.2	TSL:1 MANE Select	n.1746C>T		non_coding_transcript_exon	Exon 3 of 3
	MIR17HG	ENST00000582141.7	TSL:1	n.2131C>T		non_coding_transcript_exon	Exon 2 of 2
	MIR17HG	ENST00000400282.8	TSL:1	n.284+1329C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000118 AC: 18 AN: 152090 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000160 AC: 28 AN: 174804 Hom.: 0 Cov.: 0 AF XY: 0.000202 AC XY: 19 AN XY: 93920

African (AFR) AF: 0.00 AC: 0 AN: 5102

American (AMR) AF: 0.00 AC: 0 AN: 12972

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4088

East Asian (EAS) AF: 0.00226 AC: 18 AN: 7974

South Asian (SAS) AF: 0.0000596 AC: 2 AN: 33566

European-Finnish (FIN) AF: 0.0000706 AC: 1 AN: 14170

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 554

European-Non Finnish (NFE) AF: 0.0000568 AC: 5 AN: 88096

Other (OTH) AF: 0.000241 AC: 2 AN: 8282

GnomAD4 genome AF: 0.000112 AC: 17 AN: 152208 Hom.: 0 Cov.: 33 AF XY: 0.0000806 AC XY: 6 AN XY: 74406

African (AFR) AF: 0.0000241 AC: 1 AN: 41542

American (AMR) AF: 0.0000654 AC: 1 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00212 AC: 11 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10568

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.000132

Asia WGS AF: 0.00144 AC: 5 AN: 3478

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	-0.68
CADD	Benign	3.4
DANN	Benign	0.66
PhyloP100		-0.74
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.2

Splicing

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

Other links and lift over

dbSNP: rs139418718; hg19: chr13-92003809;