Genetic Variant ENST00000384994.1:n.51G>T (chr11-65444508-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000384994.1(MIR612):n.51G>T 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 0.00000295 in 338,730 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: 30)

Exomes 𝑓: 0.0000030 ( 0 hom. )

Consequence

MIR612
ENST00000384994.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.44

Publications

0 publications found

Variant links:

Genes affected

MIR612 (HGNC:32868): (microRNA 612) 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]

MIR612 links:

NEAT1 (HGNC:30815): (nuclear paraspeckle assembly transcript 1) This gene produces a long non-coding RNA (lncRNA) transcribed from the multiple endocrine neoplasia locus. This lncRNA is retained in the nucleus where it forms the core structural component of the paraspeckle sub-organelles. It may act as a transcriptional regulator for numerous genes, including some genes involved in cancer progression. [provided by RefSeq, Mar 2015]

NEAT1 links:

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ACMG classification

Classification was made for transcript

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=-0.76).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
MIR612	NR_030343.1 link	n.51G>T	non_coding_transcript_exon_variant	Exon 1 of 1
NEAT1	NR_131012.1 link	n.21711G>T	non_coding_transcript_exon_variant	Exon 1 of 1
MIR612	unassigned_transcript_1908	n.*11G>T	downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIR612	ENST00000384994.1 link	n.51G>T		non_coding_transcript_exon_variant	Exon 1 of 1	6
NEAT1	ENST00000501122.4 link	n.21711G>T		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000295

AC:

AN:

338730

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

191818

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

9418

American (AMR)

AF:

0.00

AC:

AN:

29890

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10962

East Asian (EAS)

AF:

0.0000927

AC:

AN:

10782

South Asian (SAS)

AF:

0.00

AC:

AN:

61212

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29306

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2812

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

169314

Other (OTH)

AF:

0.00

AC:

AN:

15034

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

7.6

(source)

DANN

Benign

0.81

PhyloP100

1.4

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.3

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over