Genetic Variant MIR1-1HG:n.794-179G>A (chr20-62564810-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000624914.4(MIR1-1HG):n.794-179G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 363,416 control chromosomes in the GnomAD database, including 10,295 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 0.25 ( 5181 hom., cov: 35)

Exomes 𝑓: 0.21 ( 5114 hom. )

Consequence

MIR1-1HG
ENST00000624914.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.809

Variant links:

Genes affected

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

MIR1-1HG links:

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]

MIR133A2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
MIR1-1HG	ENST00000624914.4 link	n.794-179G>A	intron_variant	Intron 2 of 3	1
MIR1-1HG	ENST00000370523.3 link	n.242-5634G>A	intron_variant	Intron 2 of 2	5
MIR1-1HG	ENST00000686477.1 link	n.792-5634G>A	intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.255

AC:

38734

AN:

152046

Hom.:

5180

Cov.:

show subpopulations

Gnomad AFR

AF:

0.342

Gnomad AMI

AF:

0.137

Gnomad AMR

AF:

0.257

Gnomad ASJ

AF:

0.181

Gnomad EAS

AF:

0.169

Gnomad SAS

AF:

0.178

Gnomad FIN

AF:

0.187

Gnomad MID

AF:

0.258

Gnomad NFE

AF:

0.229

Gnomad OTH

AF:

0.246

GnomAD4 exome

AF:

0.215

AC:

45409

AN:

211252

Hom.:

5114

AF XY:

0.211

AC XY:

24335

AN XY:

115092

show subpopulations

African (AFR)

AF:

0.343

AC:

1727

AN:

5034

American (AMR)

AF:

0.239

AC:

2419

AN:

10112

Ashkenazi Jewish (ASJ)

AF:

0.170

AC:

756

AN:

4444

East Asian (EAS)

AF:

0.173

AC:

1272

AN:

7370

South Asian (SAS)

AF:

0.184

AC:

7855

AN:

42784

European-Finnish (FIN)

AF:

0.188

AC:

4476

AN:

23776

Middle Eastern (MID)

AF:

0.240

AC:

155

AN:

646

European-Non Finnish (NFE)

AF:

0.229

AC:

24716

AN:

107720

Other (OTH)

AF:

0.217

AC:

2033

AN:

9366

Heterozygous variant carriers

1587

3175

4762

6350

7937

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

200

400

600

800

1000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.255

AC:

38757

AN:

152164

Hom.:

5181

Cov.:

AF XY:

0.253

AC XY:

18823

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.341

AC:

14173

AN:

41510

American (AMR)

AF:

0.258

AC:

3939

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.181

AC:

628

AN:

3472

East Asian (EAS)

AF:

0.169

AC:

875

AN:

5178

South Asian (SAS)

AF:

0.177

AC:

855

AN:

4832

European-Finnish (FIN)

AF:

0.187

AC:

1977

AN:

10592

Middle Eastern (MID)

AF:

0.253

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.229

AC:

15595

AN:

67980

Other (OTH)

AF:

0.245

AC:

517

AN:

2112

Heterozygous variant carriers

1501

3002

4504

6005

7506

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

404

808

1212

1616

2020

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.242

Hom.:

554

Bravo

AF:

0.263

Asia WGS

AF:

0.139

AC:

484

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

9.3

DANN

Benign

0.75

Mutation Taster

=100/0

polymorphism (auto)

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over