20-62564810-G-T

Variant names:

• chr20-62564810-G-T
• rs45547937
• ENST00000624914.4:n.794-179G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000624914.4(MIR1-1HG):​n.794-179G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000472 in 211,644 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 35)
  • Exomes 𝑓: 0.0000047 (0 hom.)
• Consequence: MIR1-1HG ENST00000624914.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.809

Genes affected

MIR1-1HG (HGNC:16159): (MIR1-1 host gene)

MIR133A2 (HGNC:31518): (microRNA 133a-2) 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIR1-1HG	NR_171007.1	n.788-179G>T		intron_variant	Intron 2 of 3
MIR133A2	NR_029676.1	n.-102G>T		upstream_gene_variant
MIR133A2	unassigned_transcript_3477	n.-123G>T		upstream_gene_variant
MIR133A2	unassigned_transcript_3478	n.-160G>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIR1-1HG	ENST00000624914.4	n.794-179G>T		intron_variant	Intron 2 of 3	1
MIR1-1HG	ENST00000370523.3	n.242-5634G>T		intron_variant	Intron 2 of 2	5
MIR1-1HG	ENST00000686477.1	n.792-5634G>T		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome AF: 0.00000472 AC: 1 AN: 211644 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 115270

African (AFR) AF: 0.00 AC: 0 AN: 5050

American (AMR) AF: 0.00 AC: 0 AN: 10148

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4450

East Asian (EAS) AF: 0.000136 AC: 1 AN: 7380

South Asian (SAS) AF: 0.00 AC: 0 AN: 42842

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23796

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 648

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 107940

Other (OTH) AF: 0.00 AC: 0 AN: 9390

⚠️ The allele balance in gnomAD4 Exomes is highly skewed (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.3
DANN	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs45547937; hg19: chr20-61162017;