rs41292412

Variant names:

• chr18-58451126-C-T
• rs41292412
• ENST00000385044.3:n.53C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The ENST00000590797.5(MIR122HG):​n.2292C>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: MIR122HG ENST00000590797.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.03
• Publications: 16 publications found

Genes affected

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]

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

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

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.17).
• BS2: High Homozygotes in GnomAd4 at 8 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000590797.5. 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
	MIR122	NR_029667.1		n.53C>T		non_coding_transcript_exon	Exon 1 of 1
	MIR3591	NR_039899.1		n.27G>A		non_coding_transcript_exon	Exon 1 of 1
	MIR122HG	NR_170244.1		n.453C>T		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR122	ENST00000385044.3	TSL:6	n.53C>T		non_coding_transcript_exon	Exon 1 of 1
	MIR122HG	ENST00000590797.5	TSL:2	n.2292C>T		non_coding_transcript_exon	Exon 2 of 2
	MIR3591	ENST00000636727.1	TSL:6	n.27G>A		non_coding_transcript_exon	Exon 1 of 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

GnomAD2 exomes AF: 0.00584 AC: 1327 AN: 227340 AF XY: 0.00575

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 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

African (AFR) AF: 0.00213 AC: 22 AN: 10322

American (AMR) AF: 0.00209 AC: 74 AN: 35372

Ashkenazi Jewish (ASJ) AF: 0.00187 AC: 21 AN: 11212

East Asian (EAS) AF: 0.00 AC: 0 AN: 13026

South Asian (SAS) AF: 0.000465 AC: 30 AN: 64510

European-Finnish (FIN) AF: 0.0102 AC: 321 AN: 31318

Middle Eastern (MID) AF: 0.00178 AC: 5 AN: 2816

European-Non Finnish (NFE) AF: 0.00963 AC: 1751 AN: 181874

Other (OTH) AF: 0.00626 AC: 100 AN: 15980

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

African (AFR) AF: 0.00214 AC: 89 AN: 41546

American (AMR) AF: 0.00386 AC: 59 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5194

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.0121 AC: 128 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00932 AC: 634 AN: 68026

Other (OTH) AF: 0.00616 AC: 13 AN: 2112

Alfa AF: 0.00811 Hom.: 13

Bravo AF: 0.00621

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.17
CADD	Benign	22
DANN	Benign	0.91
PhyloP100		6.0

Splicing

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

Other links and lift over

dbSNP: rs41292412; hg19: chr18-56118358;