Genetic Variant MIR1208:n.5G>C (chr8-128150120-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000408334.1(MIR1208):n.5G>C 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 0.00266 in 523,052 control chromosomes in the GnomAD database, including 46 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 0.0023 ( 16 hom., cov: 32)

Exomes 𝑓: 0.0028 ( 30 hom. )

Consequence

MIR1208
ENST00000408334.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.404

Publications

6 publications found

Variant links:

Genes affected

MIR1208 (HGNC:35274): (microRNA 1208) 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]

MIR1208 links:

PVT1 (HGNC:9709): (Pvt1 oncogene) This gene represents a long non-coding RNA locus that has been identified as a candidate oncogene. Increased copy number and overexpression of this gene are associated with many types of cancers including breast and ovarian cancers, acute myeloid leukemia and Hodgkin lymphoma. Allelic variants of this gene are also associated with end-stage renal disease attributed to type 1 diabetes. Consistent with its association with various types of cancer, transcription of this gene is regulated by the tumor suppressor p53 through a canonical p53-binding site, and it has been implicated in regulating levels of the proto-oncogene MYC to promote tumorigenesis. [provided by RefSeq, Sep 2015]

PVT1 links:

ENSG00000309955 (HGNC:):

ENSG00000309955 links:

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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=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.054 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIR1208	NR_031613.1 link	n.5G>C		non_coding_transcript_exon_variant	Exon 1 of 1
MIR1208	unassigned_transcript_1536	n.-7G>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
MIR1208	ENST00000408334.1 link	n.5G>C	non_coding_transcript_exon_variant	Exon 1 of 1	6
PVT1	ENST00000650846.1 link	n.403+2132G>C	intron_variant	Intron 2 of 3
PVT1	ENST00000651587.1 link	n.1378+2132G>C	intron_variant	Intron 7 of 10

Frequencies

GnomAD3 genomes

AF:

0.00233

AC:

355

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0599

Gnomad SAS

AF:

0.00353

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.00519

AC:

1215

AN:

233930

AF XY:

0.00473

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000950

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0684

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000207

Gnomad OTH exome

AF:

0.00214

GnomAD4 exome

AF:

0.00280

AC:

1039

AN:

370804

Hom.:

Cov.:

AF XY:

0.00281

AC XY:

596

AN XY:

211980

show subpopulations

African (AFR)

AF:

0.000104

AC:

AN:

9618

American (AMR)

AF:

0.000116

AC:

AN:

34406

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11558

East Asian (EAS)

AF:

0.0675

AC:

773

AN:

11444

South Asian (SAS)

AF:

0.00283

AC:

184

AN:

65018

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32180

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2832

European-Non Finnish (NFE)

AF:

0.000219

AC:

AN:

187486

Other (OTH)

AF:

0.00221

AC:

AN:

16262

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

143

191

239

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<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:

0.00233

AC:

354

AN:

152248

Hom.:

Cov.:

AF XY:

0.00246

AC XY:

183

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41538

American (AMR)

AF:

0.000654

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.0594

AC:

308

AN:

5184

South Asian (SAS)

AF:

0.00353

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000176

AC:

AN:

68016

Other (OTH)

AF:

0.00237

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.000287

Hom.:

Bravo

AF:

0.00295

Asia WGS

AF:

0.0220

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

5.3

(source)

DANN

Benign

0.49

PhyloP100

-0.40

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over