10-133247608-C-T

Variant names:

• chr10-133247608-C-T
• rs12355840
• ENST00000300167.8:n.221G>A

Variant summary

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

The ENST00000300167.8(MIR202HG):​n.221G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.779 in 459,196 control chromosomes in the GnomAD database, including 145,790 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 0.69 (40561 hom., cov: 33)
  • Exomes 𝑓: 0.82 (105229 hom.)
• Consequence: MIR202HG ENST00000300167.8 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.223
• Publications: 36 publications found

Genes affected

MIR202HG (HGNC:49402): (MIR202 host gene)

MIR202 (HGNC:32080): (microRNA 202) 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.886 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIR202	NR_030170.1	n.13G>A		non_coding_transcript_exon_variant	Exon 1 of 1
MIR202HG	NR_108078.1	n.189G>A		non_coding_transcript_exon_variant	Exon 2 of 3
MIR202HG	NR_108079.1	n.95+183G>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIR202HG	ENST00000300167.8	n.221G>A		non_coding_transcript_exon_variant	Exon 2 of 3	2
MIR202	ENST00000362219.2	n.13G>A		non_coding_transcript_exon_variant	Exon 1 of 1	6
MIR202HG	ENST00000669738.2	n.286G>A		non_coding_transcript_exon_variant	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.694 AC: 105402 AN: 151952 Hom.: 40550 Cov.: 33

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.722

Gnomad ASJ AF: 0.764

Gnomad EAS AF: 0.908

Gnomad SAS AF: 0.811

Gnomad FIN AF: 0.876

Gnomad MID AF: 0.745

Gnomad NFE AF: 0.848

Gnomad OTH AF: 0.700

GnomAD2 exomes AF: 0.800 AC: 123618 AN: 154602 AF XY: 0.810

Gnomad AFR exome AF: 0.317

Gnomad AMR exome AF: 0.742

Gnomad ASJ exome AF: 0.759

Gnomad EAS exome AF: 0.919

Gnomad FIN exome AF: 0.875

Gnomad NFE exome AF: 0.849

Gnomad OTH exome AF: 0.804

GnomAD4 exome AF: 0.821 AC: 252238 AN: 307128 Hom.: 105229 Cov.: 0 AF XY: 0.824 AC XY: 143516 AN XY: 174078

African (AFR) AF: 0.329 AC: 2782 AN: 8460

American (AMR) AF: 0.739 AC: 20091 AN: 27182

Ashkenazi Jewish (ASJ) AF: 0.762 AC: 7935 AN: 10410

East Asian (EAS) AF: 0.918 AC: 8321 AN: 9066

South Asian (SAS) AF: 0.821 AC: 48289 AN: 58816

European-Finnish (FIN) AF: 0.879 AC: 24090 AN: 27410

Middle Eastern (MID) AF: 0.739 AC: 1850 AN: 2502

European-Non Finnish (NFE) AF: 0.856 AC: 128179 AN: 149780

Other (OTH) AF: 0.793 AC: 10701 AN: 13502

GnomAD4 genome AF: 0.693 AC: 105430 AN: 152068 Hom.: 40561 Cov.: 33 AF XY: 0.700 AC XY: 52057 AN XY: 74354

African (AFR) AF: 0.333 AC: 13817 AN: 41474

American (AMR) AF: 0.722 AC: 11049 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.764 AC: 2648 AN: 3468

East Asian (EAS) AF: 0.908 AC: 4689 AN: 5166

South Asian (SAS) AF: 0.813 AC: 3920 AN: 4824

European-Finnish (FIN) AF: 0.876 AC: 9279 AN: 10596

Middle Eastern (MID) AF: 0.740 AC: 216 AN: 292

European-Non Finnish (NFE) AF: 0.848 AC: 57594 AN: 67928

Other (OTH) AF: 0.703 AC: 1485 AN: 2112

Alfa AF: 0.650 Hom.: 10929

Bravo AF: 0.666

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.8
DANN	Benign	0.90
PhyloP100		0.22

Splicing

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

Other links and lift over

dbSNP: rs12355840; hg19: chr10-135061112;