11-122100038-T-G

Variant names:

• chr11-122100038-T-G
• rs2081443
• ENST00000524376.3:n.128+336A>C

Variant summary

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

The ENST00000524376.3(MIR100HG):​n.128+336A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 152,130 control chromosomes in the GnomAD database, including 2,515 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 0.18 (2515 hom., cov: 32)
• Consequence: MIR100HG ENST00000524376.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.328
• Publications: 9 publications found

Genes affected

MIR100HG (HGNC:39522): (mir-100-let-7a-2-mir-125b-1 cluster host gene) This gene produces long non-coding RNAs that act as regulators of cell proliferation. Alternative promoter usage and splicing results in multiple transcript variants. Some transcript variants may promote growth, while others may act to negatively regulate cell division. [provided by RefSeq, May 2016]

MIR125B1 (HGNC:31506): (microRNA 125b-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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000524376.3. 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
	MIR100HG	NR_024430.2		n.492-8298A>C		intron	N/A
	MIR100HG	NR_137175.1		n.783+1409A>C		intron	N/A
	MIR100HG	NR_137176.1		n.473+336A>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR100HG	ENST00000524376.3	TSL:1	n.128+336A>C		intron	N/A
	MIR100HG	ENST00000528986.2	TSL:1	n.896+336A>C		intron	N/A
	MIR100HG	ENST00000534782.4	TSL:1	n.388-8319A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26982 AN: 152012 Hom.: 2512 Cov.: 32

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.177 AC: 26998 AN: 152130 Hom.: 2515 Cov.: 32 AF XY: 0.177 AC XY: 13183 AN XY: 74384

African (AFR) AF: 0.147 AC: 6102 AN: 41506

American (AMR) AF: 0.201 AC: 3083 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 366 AN: 3466

East Asian (EAS) AF: 0.298 AC: 1545 AN: 5176

South Asian (SAS) AF: 0.238 AC: 1145 AN: 4810

European-Finnish (FIN) AF: 0.164 AC: 1732 AN: 10580

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.183 AC: 12459 AN: 67978

Other (OTH) AF: 0.180 AC: 380 AN: 2108

Alfa AF: 0.177 Hom.: 4826

Bravo AF: 0.182

Asia WGS AF: 0.258 AC: 896 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	6.4
DANN	Benign	0.67
PhyloP100		-0.33

Splicing

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

Other links and lift over

dbSNP: rs2081443; hg19: chr11-121970746;