ENST00000413053.2:n.2280C>A

Variant names:

• chr11-64890927-G-T
• rs7949144
• ENST00000413053.2:n.2280C>A

Variant summary

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

The ENST00000413053.2(MIR194-2HG):​n.2280C>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 0.000011 in 90,974 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: 31)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: MIR194-2HG ENST00000413053.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.75
• Publications: 0 publications found

Genes affected

MIR194-2HG (HGNC:51946): (MIR194-2 host gene)

MIR192 (HGNC:31562): (microRNA 192) 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=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIR194-2HG	NR_133638.1	n.2280C>A		non_coding_transcript_exon_variant	Exon 2 of 2
MIR194-2HG	NR_133639.1	n.437+1502C>A		intron_variant	Intron 2 of 2
MIR194-2HG	NR_133640.1	n.277-1587C>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIR194-2HG	ENST00000413053.2	n.2280C>A		non_coding_transcript_exon_variant	Exon 2 of 2	2
MIR194-2HG	ENST00000710929.1	n.391-1587C>A		intron_variant	Intron 3 of 3
MIR194-2HG	ENST00000710930.1	n.551+1502C>A		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.0000110 AC: 1 AN: 90974 Hom.: 0 Cov.: 0 AF XY: 0.0000198 AC XY: 1 AN XY: 50624

African (AFR) AF: 0.00 AC: 0 AN: 1150

American (AMR) AF: 0.00 AC: 0 AN: 3860

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1736

East Asian (EAS) AF: 0.00 AC: 0 AN: 1250

South Asian (SAS) AF: 0.00 AC: 0 AN: 21768

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5422

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 340

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 51016

Other (OTH) AF: 0.000226 AC: 1 AN: 4432

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.8
DANN	Benign	0.62
PhyloP100		1.8

Splicing

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

Other links and lift over

dbSNP: rs7949144; hg19: chr11-64658399;