rs41292412

chr18-58451126-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4 BS2

The NR_029667.1(MIR122):n.53C>T variant causes a non coding transcript exon change. The variant allele was found at a frequency of 0.0064 in 518,710 control chromosomes in the GnomAD database, including 27 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 0.0065 (8 hom., cov: 32)
  • Exomes 𝑓: 0.0063 (19 hom.)
• Consequence: MIR122 NR_029667.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.03

Genes affected

MIR122HG (HGNC:53821): (MIR122 host gene)

MIR122 (HGNC:31501): (microRNA 122) 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]

MIR3591 (HGNC:41875): (microRNA 3591) 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 Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.17).
• BS2: High Homozygotes in GnomAd at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MIR122	NR_029667.1	n.53C>T		non_coding_transcript_exon_variant	1/1
MIR3591	NR_039899.1	n.27G>A		non_coding_transcript_exon_variant	1/1
MIR122HG	NR_170245.1	n.615C>T		non_coding_transcript_exon_variant	3/3
MIR122HG	NR_170244.1	n.453C>T		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIR122HG	ENST00000590797.4	n.1913C>T		non_coding_transcript_exon_variant	2/2	2
MIR122	ENST00000385044.3	n.53C>T		mature_miRNA_variant	1/1
MIR3591	ENST00000636727.1	n.27G>A		mature_miRNA_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.00655 AC: 997 AN: 152162 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.00215

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.00386

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0121

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00932

Gnomad OTH AF: 0.00622

GnomAD3 exomes AF: 0.00584 AC: 1327 AN: 227340 Hom.: 20 AF XY: 0.00575 AC XY: 703 AN XY: 122204

Gnomad AFR exome AF: 0.00146

Gnomad AMR exome AF: 0.00207

Gnomad ASJ exome AF: 0.00203

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000286

Gnomad FIN exome AF: 0.0110

Gnomad NFE exome AF: 0.00982

Gnomad OTH exome AF: 0.00352

GnomAD4 exome AF: 0.00634 AC: 2324 AN: 366430 Hom.: 19 Cov.: 0 AF XY: 0.00586 AC XY: 1219 AN XY: 208082

Gnomad4 AFR exome AF: 0.00213

Gnomad4 AMR exome AF: 0.00209

Gnomad4 ASJ exome AF: 0.00187

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000465

Gnomad4 FIN exome AF: 0.0102

Gnomad4 NFE exome AF: 0.00963

Gnomad4 OTH exome AF: 0.00626

GnomAD4 genome AF: 0.00655 AC: 997 AN: 152280 Hom.: 8 Cov.: 32 AF XY: 0.00685 AC XY: 510 AN XY: 74456

Gnomad4 AFR AF: 0.00214

Gnomad4 AMR AF: 0.00386

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.0121

Gnomad4 NFE AF: 0.00932

Gnomad4 OTH AF: 0.00616

Alfa AF: 0.00763 Hom.: 5

Bravo AF: 0.00621

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.17
Cadd	Benign	22
Dann	Benign	0.91

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs41292412; hg19: chr18-56118358;