11-122152219-C-T

Variant names:

• chr11-122152219-C-T
• rs543412
• ENST00000534782.4:n.387+28117G>A

Variant summary

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

The ENST00000534782.4(MIR100HG):​n.387+28117G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 534,108 control chromosomes in the GnomAD database, including 28,618 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 0.32 (7956 hom., cov: 32)
  • Exomes 𝑓: 0.32 (20662 hom.)
• Consequence: MIR100HG ENST00000534782.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05
• Publications: 25 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]

MIR10526 (HGNC:54016): (microRNA 10526) 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]

MIR100 (HGNC:31487): (microRNA 100) 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=-0.74).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIR100HG	NR_024430.2	n.491+3332G>A		intron_variant	Intron 3 of 3
MIR100HG	NR_137179.1	n.445+3332G>A		intron_variant	Intron 4 of 4
MIR100HG	NR_137180.1	n.503+3332G>A		intron_variant	Intron 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIR100HG	ENST00000534782.4	n.387+28117G>A		intron_variant	Intron 2 of 2	1
MIR100HG	ENST00000534297.2	n.185+3332G>A		intron_variant	Intron 2 of 3	4
MIR100HG	ENST00000637700.1	n.681+3332G>A		intron_variant	Intron 5 of 5	5

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48369 AN: 151924 Hom.: 7950 Cov.: 32

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.331

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.311

GnomAD2 exomes AF: 0.316 AC: 79150 AN: 250372 AF XY: 0.323

Gnomad AFR exome AF: 0.365

Gnomad AMR exome AF: 0.256

Gnomad ASJ exome AF: 0.342

Gnomad EAS exome AF: 0.393

Gnomad FIN exome AF: 0.234

Gnomad NFE exome AF: 0.294

Gnomad OTH exome AF: 0.315

GnomAD4 exome AF: 0.319 AC: 121881 AN: 382066 Hom.: 20662 Cov.: 0 AF XY: 0.331 AC XY: 72009 AN XY: 217504

African (AFR) AF: 0.368 AC: 3865 AN: 10498

American (AMR) AF: 0.260 AC: 9414 AN: 36246

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 3974 AN: 11726

East Asian (EAS) AF: 0.399 AC: 5257 AN: 13164

South Asian (SAS) AF: 0.443 AC: 29532 AN: 66690

European-Finnish (FIN) AF: 0.237 AC: 7644 AN: 32292

Middle Eastern (MID) AF: 0.334 AC: 952 AN: 2848

European-Non Finnish (NFE) AF: 0.292 AC: 56029 AN: 191888

Other (OTH) AF: 0.312 AC: 5214 AN: 16714

GnomAD4 genome AF: 0.318 AC: 48404 AN: 152042 Hom.: 7956 Cov.: 32 AF XY: 0.317 AC XY: 23597 AN XY: 74328

African (AFR) AF: 0.369 AC: 15310 AN: 41456

American (AMR) AF: 0.267 AC: 4085 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 1122 AN: 3464

East Asian (EAS) AF: 0.410 AC: 2117 AN: 5166

South Asian (SAS) AF: 0.448 AC: 2155 AN: 4812

European-Finnish (FIN) AF: 0.230 AC: 2434 AN: 10580

Middle Eastern (MID) AF: 0.332 AC: 97 AN: 292

European-Non Finnish (NFE) AF: 0.298 AC: 20257 AN: 67974

Other (OTH) AF: 0.309 AC: 653 AN: 2112

Alfa AF: 0.316 Hom.: 5701

Bravo AF: 0.319

Asia WGS AF: 0.413 AC: 1436 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	15
DANN	Benign	0.60
PhyloP100		1.1
Mutation Taster		=98/2	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs543412; hg19: chr11-122022927; COSMIC: COSV66115284;