rs2241490

Variant names:

• chr11-122100072-C-T
• rs2241490
• ENST00000524376.3:n.128+302G>A

Variant summary

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

The ENST00000524376.3(MIR100HG):​n.128+302G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 152,170 control chromosomes in the GnomAD database, including 4,213 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 0.22 (4213 hom., cov: 32)
• Consequence: MIR100HG ENST00000524376.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24
• Publications: 10 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=-0.64).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.323 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.492-8332G>A		intron	N/A
	MIR100HG	NR_137175.1		n.783+1375G>A		intron	N/A
	MIR100HG	NR_137176.1		n.473+302G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR100HG	ENST00000524376.3	TSL:1	n.128+302G>A		intron	N/A
	MIR100HG	ENST00000528986.2	TSL:1	n.896+302G>A		intron	N/A
	MIR100HG	ENST00000534782.4	TSL:1	n.388-8353G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33799 AN: 152052 Hom.: 4214 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.375

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.337

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.222 AC: 33811 AN: 152170 Hom.: 4213 Cov.: 32 AF XY: 0.226 AC XY: 16845 AN XY: 74392

African (AFR) AF: 0.102 AC: 4229 AN: 41542

American (AMR) AF: 0.219 AC: 3346 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 957 AN: 3468

East Asian (EAS) AF: 0.336 AC: 1740 AN: 5172

South Asian (SAS) AF: 0.311 AC: 1499 AN: 4820

European-Finnish (FIN) AF: 0.273 AC: 2885 AN: 10574

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.269 AC: 18312 AN: 67988

Other (OTH) AF: 0.209 AC: 442 AN: 2110

Alfa AF: 0.246 Hom.: 842

Bravo AF: 0.210

Asia WGS AF: 0.336 AC: 1168 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	2.1
DANN	Benign	0.94
PhyloP100		-1.2

Splicing

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

Other links and lift over

dbSNP: rs2241490; hg19: chr11-121970780;