rs2241490

Variant names:

• chr11-122100072-C-T
• rs2241490
• ENST00000524376.2:n.75+302G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000524376.2(MIR100HG):​n.75+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 ENST00000524376.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIR100HG	NR_024430.2	n.492-8332G>A		intron_variant	Intron 3 of 3
MIR100HG	NR_137175.1	n.783+1375G>A		intron_variant	Intron 1 of 1
MIR100HG	NR_137176.1	n.473+302G>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIR100HG	ENST00000524376.2	n.75+302G>A		intron_variant	Intron 1 of 1	1
MIR100HG	ENST00000528986.2	n.896+302G>A		intron_variant	Intron 2 of 2	1
MIR100HG	ENST00000534782.4	n.388-8353G>A		intron_variant	Intron 2 of 2	1

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

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.219

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.336

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.273

Gnomad4 NFE AF: 0.269

Gnomad4 OTH AF: 0.209

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 v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2241490; hg19: chr11-121970780;