chr11-64890927-G-C

Variant names:

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

Variant summary

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

The ENST00000413053.2(MIR194-2HG):​n.2280C>G 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 0.0394 in 243,176 control chromosomes in the GnomAD database, including 300 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 0.040 (173 hom., cov: 31)
  • Exomes 𝑓: 0.039 (127 hom.)
• Consequence: MIR194-2HG ENST00000413053.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.75

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIR194-2HG	NR_133638.1	n.2280C>G		non_coding_transcript_exon_variant	Exon 2 of 2
MIR194-2HG	NR_133639.1	n.437+1502C>G		intron_variant	Intron 2 of 2
MIR194-2HG	NR_133640.1	n.277-1587C>G		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>G		non_coding_transcript_exon_variant	Exon 2 of 2	2
MIR194-2HG	ENST00000710929.1	n.391-1587C>G		intron_variant	Intron 3 of 3
MIR194-2HG	ENST00000710930.1	n.551+1502C>G		intron_variant	Intron 3 of 3
MIR192	ENST00000384915.3	n.*210C>G		downstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.0400 AC: 6082 AN: 152132 Hom.: 173 Cov.: 31

Gnomad AFR AF: 0.0104

Gnomad AMI AF: 0.0516

Gnomad AMR AF: 0.0378

Gnomad ASJ AF: 0.0942

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0126

Gnomad FIN AF: 0.0948

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.0513

Gnomad OTH AF: 0.0469

GnomAD4 exome AF: 0.0386 AC: 3507 AN: 90926 Hom.: 127 Cov.: 0 AF XY: 0.0354 AC XY: 1791 AN XY: 50602

Gnomad4 AFR exome AF: 0.00783

Gnomad4 AMR exome AF: 0.0293

Gnomad4 ASJ exome AF: 0.0962

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0144

Gnomad4 FIN exome AF: 0.0826

Gnomad4 NFE exome AF: 0.0434

Gnomad4 OTH exome AF: 0.0492

GnomAD4 genome AF: 0.0399 AC: 6081 AN: 152250 Hom.: 173 Cov.: 31 AF XY: 0.0413 AC XY: 3071 AN XY: 74430

Gnomad4 AFR AF: 0.0104

Gnomad4 AMR AF: 0.0377

Gnomad4 ASJ AF: 0.0942

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0124

Gnomad4 FIN AF: 0.0948

Gnomad4 NFE AF: 0.0512

Gnomad4 OTH AF: 0.0464

Alfa AF: 0.0479 Hom.: 24

Bravo AF: 0.0351

Asia WGS AF: 0.00895 AC: 31 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.0
DANN	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7949144; hg19: chr11-64658399;