ENST00000384994.1:n.51G>A

Variant names:

• chr11-65444508-G-A
• rs12803915
• ENST00000384994.1:n.51G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000384994.1(MIR612):​n.51G>A 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 0.17 in 490,522 control chromosomes in the GnomAD database, including 7,664 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 0.17 (2285 hom., cov: 30)
  • Exomes 𝑓: 0.17 (5379 hom.)
• Consequence: MIR612 ENST00000384994.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44
• Publications: 35 publications found

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]

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIR612	NR_030343.1	n.51G>A		non_coding_transcript_exon_variant	Exon 1 of 1
NEAT1	NR_131012.1	n.21711G>A		non_coding_transcript_exon_variant	Exon 1 of 1
MIR612	unassigned_transcript_1908	n.*11G>A		downstream_gene_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25323 AN: 151834 Hom.: 2283 Cov.: 30

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.194

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.159

GnomAD2 exomes AF: 0.164 AC: 29712 AN: 180892 AF XY: 0.164

Gnomad AFR exome AF: 0.116

Gnomad AMR exome AF: 0.130

Gnomad ASJ exome AF: 0.193

Gnomad EAS exome AF: 0.146

Gnomad FIN exome AF: 0.121

Gnomad NFE exome AF: 0.207

Gnomad OTH exome AF: 0.178

GnomAD4 exome AF: 0.172 AC: 58085 AN: 338566 Hom.: 5379 Cov.: 0 AF XY: 0.169 AC XY: 32339 AN XY: 191724

African (AFR) AF: 0.125 AC: 1175 AN: 9408

American (AMR) AF: 0.131 AC: 3901 AN: 29872

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 2112 AN: 10956

East Asian (EAS) AF: 0.142 AC: 1526 AN: 10768

South Asian (SAS) AF: 0.118 AC: 7251 AN: 61196

European-Finnish (FIN) AF: 0.124 AC: 3631 AN: 29300

Middle Eastern (MID) AF: 0.219 AC: 615 AN: 2812

European-Non Finnish (NFE) AF: 0.208 AC: 35157 AN: 169222

Other (OTH) AF: 0.181 AC: 2717 AN: 15032

GnomAD4 genome AF: 0.167 AC: 25341 AN: 151956 Hom.: 2285 Cov.: 30 AF XY: 0.159 AC XY: 11838 AN XY: 74264

African (AFR) AF: 0.123 AC: 5102 AN: 41452

American (AMR) AF: 0.142 AC: 2162 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 667 AN: 3464

East Asian (EAS) AF: 0.147 AC: 759 AN: 5158

South Asian (SAS) AF: 0.109 AC: 527 AN: 4822

European-Finnish (FIN) AF: 0.118 AC: 1248 AN: 10584

Middle Eastern (MID) AF: 0.195 AC: 57 AN: 292

European-Non Finnish (NFE) AF: 0.209 AC: 14188 AN: 67922

Other (OTH) AF: 0.156 AC: 328 AN: 2104

Alfa AF: 0.192 Hom.: 1501

Bravo AF: 0.170

Asia WGS AF: 0.113 AC: 396 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.7
DANN	Benign	0.79
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

Other links and lift over

dbSNP: rs12803915; hg19: chr11-65211979; COSMIC: COSV66057836;