rs12803915

Positions:

• chr11-65444508-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_030343.1(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 NR_030343.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
MIR612	NR_030343.1	n.51G>A		non_coding_transcript_exon_variant	1/1
NEAT1	NR_131012.1	n.21711G>A		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIR612	ENST00000384994.1	n.51G>A		non_coding_transcript_exon_variant	1/1
NEAT1	ENST00000501122.2	n.21711G>A		non_coding_transcript_exon_variant	1/1

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

GnomAD3 exomes AF: 0.164 AC: 29712 AN: 180892 Hom.: 2663 AF XY: 0.164 AC XY: 15893 AN XY: 96738

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 SAS exome AF: 0.118

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

Gnomad4 AFR exome AF: 0.125

Gnomad4 AMR exome AF: 0.131

Gnomad4 ASJ exome AF: 0.193

Gnomad4 EAS exome AF: 0.142

Gnomad4 SAS exome AF: 0.118

Gnomad4 FIN exome AF: 0.124

Gnomad4 NFE exome AF: 0.208

Gnomad4 OTH exome AF: 0.181

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

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.147

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.156

Alfa AF: 0.193 Hom.: 1493

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
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

LitVar

Other links and lift over

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