rs72631833

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBS1BS2

The ENST00000384958.1(MIR183):​n.51G>T variant causes a non coding transcript exon change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00199 in 529,310 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 0.0051 ( 8 hom., cov: 33)
Exomes 𝑓: 0.00071 ( 1 hom. )

Consequence

MIR183
ENST00000384958.1 non_coding_transcript_exon

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 7.33

Publications

8 publications found
Variant links:
Genes affected
MIR183 (HGNC:31554): (microRNA 183) 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]
MIR96 (HGNC:31648): (microRNA 96) 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]
MIR96 Gene-Disease associations (from GenCC):
  • autosomal dominant nonsyndromic hearing loss 50
    Inheritance: AD Classification: STRONG, MODERATE Submitted by: PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae)
  • nonsyndromic genetic hearing loss
    Inheritance: AD Classification: MODERATE Submitted by: ClinGen

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.23).
BS1
Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00514 (782/152278) while in subpopulation AFR AF = 0.0175 (727/41550). AF 95% confidence interval is 0.0164. There are 8 homozygotes in GnomAd4. There are 359 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
BS2
High Homozygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MIR183NR_029615.1 linkn.51G>T non_coding_transcript_exon_variant Exon 1 of 1
MIR96NR_029512.1 linkn.-195G>T upstream_gene_variant
MIR96unassigned_transcript_1306 n.-246G>T upstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MIR183ENST00000384958.1 linkn.51G>T non_coding_transcript_exon_variant Exon 1 of 1 6
ENSG00000286380ENST00000710872.1 linkn.431+4826G>T intron_variant Intron 1 of 1
ENSG00000304993ENST00000807590.1 linkn.174+80C>A intron_variant Intron 1 of 1
MIR96ENST00000362288.1 linkn.-195G>T upstream_gene_variant 6

Frequencies

GnomAD3 genomes
AF:
0.00512
AC:
779
AN:
152160
Hom.:
8
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0175
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00196
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.000176
Gnomad OTH
AF:
0.00526
GnomAD2 exomes
AF:
0.00147
AC:
362
AN:
245768
AF XY:
0.00109
show subpopulations
Gnomad AFR exome
AF:
0.0190
Gnomad AMR exome
AF:
0.00120
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000171
Gnomad OTH exome
AF:
0.000993
GnomAD4 exome
AF:
0.000713
AC:
269
AN:
377032
Hom.:
1
Cov.:
0
AF XY:
0.000580
AC XY:
124
AN XY:
213952
show subpopulations
African (AFR)
AF:
0.0178
AC:
186
AN:
10436
American (AMR)
AF:
0.000998
AC:
36
AN:
36074
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
11620
East Asian (EAS)
AF:
0.00
AC:
0
AN:
13032
South Asian (SAS)
AF:
0.0000152
AC:
1
AN:
65916
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
31862
Middle Eastern (MID)
AF:
0.00149
AC:
4
AN:
2686
European-Non Finnish (NFE)
AF:
0.000153
AC:
29
AN:
188932
Other (OTH)
AF:
0.000789
AC:
13
AN:
16474
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.426
Heterozygous variant carriers
0
17
34
51
68
85
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
10
20
30
40
50
<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:
0.00514
AC:
782
AN:
152278
Hom.:
8
Cov.:
33
AF XY:
0.00482
AC XY:
359
AN XY:
74458
show subpopulations
African (AFR)
AF:
0.0175
AC:
727
AN:
41550
American (AMR)
AF:
0.00196
AC:
30
AN:
15302
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5172
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4830
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10614
Middle Eastern (MID)
AF:
0.00680
AC:
2
AN:
294
European-Non Finnish (NFE)
AF:
0.000176
AC:
12
AN:
68022
Other (OTH)
AF:
0.00521
AC:
11
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
39
78
117
156
195
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
10
20
30
40
50
<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:
0.00260
Hom.:
0
Bravo
AF:
0.00583
Asia WGS
AF:
0.00115
AC:
4
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Dec 20, 2012
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

51G>T in miR183: This variant has been identified in 0.5% individuals from the 1 000Genomes project (10/2000; rs72631833). It is also located in the loop region of the miRNA and is therefore unlikely to affect target binding specificity that is determined by the seed region. In summary, this variant is likely benign. -

not provided Benign:1
Jan 13, 2019
GeneDx
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.23
CADD
Benign
21
DANN
Benign
0.92
PhyloP100
7.3

Splicing

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

Publications

Other links and lift over

dbSNP: rs72631833; hg19: chr7-129414804; API