13-91349218-A-G

Variant names:

• chr13-91349218-A-G
• rs4284505
• ENST00000400282.8:n.141-480A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000400282.8(MIR17HG):​n.141-480A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 151,896 control chromosomes in the GnomAD database, including 21,348 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 0.52 (21348 hom., cov: 32)
• Consequence: MIR17HG ENST00000400282.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.383
• Publications: 29 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, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIR17HG	NR_027349.2	n.274-480A>G		intron_variant	Intron 1 of 3
MIR17HG	NR_027350.2	n.274-480A>G		intron_variant	Intron 1 of 1
MIR17HG	NR_197388.1	n.274-480A>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIR17HG	ENST00000400282.8	n.141-480A>G		intron_variant	Intron 1 of 3	1
MIR17HG	ENST00000581816.2	n.274-480A>G		intron_variant	Intron 1 of 2	1
MIR17HG	ENST00000582141.7	n.274-480A>G		intron_variant	Intron 1 of 1	1

Frequencies

GnomAD3 genomes AF: 0.517 AC: 78456 AN: 151778 Hom.: 21339 Cov.: 32

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.654

Gnomad AMR AF: 0.610

Gnomad ASJ AF: 0.556

Gnomad EAS AF: 0.502

Gnomad SAS AF: 0.640

Gnomad FIN AF: 0.486

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.594

Gnomad OTH AF: 0.551

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

GnomAD4 genome AF: 0.517 AC: 78479 AN: 151896 Hom.: 21348 Cov.: 32 AF XY: 0.516 AC XY: 38314 AN XY: 74252

African (AFR) AF: 0.342 AC: 14158 AN: 41450

American (AMR) AF: 0.611 AC: 9324 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.556 AC: 1925 AN: 3464

East Asian (EAS) AF: 0.502 AC: 2578 AN: 5140

South Asian (SAS) AF: 0.640 AC: 3085 AN: 4820

European-Finnish (FIN) AF: 0.486 AC: 5129 AN: 10546

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.594 AC: 40359 AN: 67894

Other (OTH) AF: 0.550 AC: 1158 AN: 2104

Alfa AF: 0.575 Hom.: 12930

Bravo AF: 0.517

Asia WGS AF: 0.518 AC: 1802 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.3
DANN	Benign	0.54
PhyloP100		-0.38
RBP_binding_hub_radar		0.0
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: rs4284505; hg19: chr13-92001472; COSMIC: COSV63011082;