rs6122014

Variant names:

• chr20-62554308-G-A
• rs6122014
• ENST00000624914.4:n.793+643G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The NR_029780.1(MIR1-1):​n.3G>A variant causes a non coding transcript exon change. The variant allele was found at a frequency of 0.00218 in 522,358 control chromosomes in the GnomAD database, including 9 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 0.0058 (9 hom., cov: 33)
  • Exomes 𝑓: 0.00069 (0 hom.)
• Consequence: MIR1-1 NR_029780.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.02
• Publications: 8 publications found

Genes affected

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

MIR1-1 (HGNC:31499): (microRNA 1-1) 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0058 (883/152324) while in subpopulation AFR AF = 0.0202 (840/41568). AF 95% confidence interval is 0.0191. There are 9 homozygotes in GnomAd4. There are 404 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NR_029780.1. 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
	MIR1-1	NR_029780.1		n.3G>A		non_coding_transcript_exon	Exon 1 of 1
	MIR1-1HG	NR_171007.1		n.787+643G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR1-1HG	ENST00000624914.4	TSL:1	n.793+643G>A		intron	N/A
	MIR1-1	ENST00000362147.2	TSL:6	n.3G>A		non_coding_transcript_exon	Exon 1 of 1
	MIR1-1HG	ENST00000370523.4	TSL:5	n.243+643G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00576 AC: 877 AN: 152206 Hom.: 9 Cov.: 33

Gnomad AFR AF: 0.0201

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00242

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00148 AC: 371 AN: 250398 AF XY: 0.00105

Gnomad AFR exome AF: 0.0201

Gnomad AMR exome AF: 0.000927

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000707

Gnomad OTH exome AF: 0.000982

GnomAD4 exome AF: 0.000689 AC: 255 AN: 370034 Hom.: 0 Cov.: 0 AF XY: 0.000463 AC XY: 97 AN XY: 209638

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0197 AC: 202 AN: 10270

American (AMR) AF: 0.000885 AC: 32 AN: 36152

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11558

East Asian (EAS) AF: 0.00 AC: 0 AN: 12798

South Asian (SAS) AF: 0.0000453 AC: 3 AN: 66158

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31692

Middle Eastern (MID) AF: 0.000797 AC: 2 AN: 2508

European-Non Finnish (NFE) AF: 0.0000164 AC: 3 AN: 182776

Other (OTH) AF: 0.000806 AC: 13 AN: 16122

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00580 AC: 883 AN: 152324 Hom.: 9 Cov.: 33 AF XY: 0.00542 AC XY: 404 AN XY: 74500

African (AFR) AF: 0.0202 AC: 840 AN: 41568

American (AMR) AF: 0.00242 AC: 37 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68016

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.00192 Hom.: 1

Bravo AF: 0.00693

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	20
DANN	Benign	0.91
PhyloP100		4.0
Mutation Taster		=97/3	polymorphism

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6122014;

hg19: chr20-61151515;