ENST00000501122.4:n.21672C>A

Variant names:

• chr11-65444469-C-A
• rs550894
• ENST00000501122.4:n.21672C>A

Variant summary

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

The ENST00000501122.4(NEAT1):​n.21672C>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 0.155 in 473,128 control chromosomes in the GnomAD database, including 8,503 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 0.13 (1816 hom., cov: 30)
  • Exomes 𝑓: 0.17 (6687 hom.)
• Consequence: NEAT1 ENST00000501122.4 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.548
• Publications: 23 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000501122.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEAT1	NR_131012.1	MANE Select	n.21672C>A		non_coding_transcript_exon	Exon 1 of 1
	MIR612	NR_030343.1		n.12C>A		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEAT1	ENST00000501122.4	TSL:6 MANE Select	n.21672C>A		non_coding_transcript_exon	Exon 1 of 1
	MIR612	ENST00000384994.1	TSL:6	n.12C>A		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20339 AN: 151968 Hom.: 1819 Cov.: 30

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.0756

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0989

Gnomad OTH AF: 0.155

GnomAD2 exomes AF: 0.193 AC: 30359 AN: 157176 AF XY: 0.190

Gnomad AFR exome AF: 0.125

Gnomad AMR exome AF: 0.441

Gnomad ASJ exome AF: 0.143

Gnomad EAS exome AF: 0.247

Gnomad FIN exome AF: 0.0782

Gnomad NFE exome AF: 0.101

Gnomad OTH exome AF: 0.158

GnomAD4 exome AF: 0.165 AC: 53121 AN: 321042 Hom.: 6687 Cov.: 0 AF XY: 0.170 AC XY: 30856 AN XY: 181400

African (AFR) AF: 0.124 AC: 1076 AN: 8690

American (AMR) AF: 0.445 AC: 12166 AN: 27334

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 1502 AN: 10778

East Asian (EAS) AF: 0.250 AC: 2342 AN: 9356

South Asian (SAS) AF: 0.264 AC: 15769 AN: 59840

European-Finnish (FIN) AF: 0.0766 AC: 2169 AN: 28316

Middle Eastern (MID) AF: 0.120 AC: 333 AN: 2784

European-Non Finnish (NFE) AF: 0.0987 AC: 15744 AN: 159560

Other (OTH) AF: 0.140 AC: 2020 AN: 14384

GnomAD4 genome AF: 0.134 AC: 20348 AN: 152086 Hom.: 1816 Cov.: 30 AF XY: 0.140 AC XY: 10388 AN XY: 74316

African (AFR) AF: 0.118 AC: 4881 AN: 41500

American (AMR) AF: 0.295 AC: 4502 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 488 AN: 3466

East Asian (EAS) AF: 0.246 AC: 1271 AN: 5160

South Asian (SAS) AF: 0.267 AC: 1286 AN: 4818

European-Finnish (FIN) AF: 0.0756 AC: 801 AN: 10590

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0989 AC: 6720 AN: 67970

Other (OTH) AF: 0.153 AC: 323 AN: 2106

Alfa AF: 0.111 Hom.: 466

Bravo AF: 0.151

Asia WGS AF: 0.253 AC: 878 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	6.5
DANN	Benign	0.61
PhyloP100		0.55
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

Splicing

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

Other links and lift over

dbSNP: rs550894; hg19: chr11-65211940; COSMIC: COSV66057916;