11-65444508-G-T

Variant names:

• chr11-65444508-G-T
• rs12803915
• ENST00000501122.4:n.21711G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NR_030343.1(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 NR_030343.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44
• Publications: 0 publications found

Genes affected

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]

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]

ACMG classification

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).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NR_030343.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEAT1	NR_131012.1	MANE Select	n.21711G>T		non_coding_transcript_exon	Exon 1 of 1
	MIR612	NR_030343.1		n.51G>T		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEAT1	ENST00000501122.4	TSL:6 MANE Select	n.21711G>T		non_coding_transcript_exon	Exon 1 of 1
	MIR612	ENST00000384994.1	TSL:6	n.51G>T		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000295 AC: 1 AN: 338730 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 191818

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

African (AFR) AF: 0.00 AC: 0 AN: 9418

American (AMR) AF: 0.00 AC: 0 AN: 29890

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10962

East Asian (EAS) AF: 0.0000927 AC: 1 AN: 10782

South Asian (SAS) AF: 0.00 AC: 0 AN: 61212

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29306

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2812

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 169314

Other (OTH) AF: 0.00 AC: 0 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.

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.6
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

Other links and lift over

dbSNP: rs12803915; hg19: chr11-65211979;