rs41274312

Positions:

• chr18-35904829-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The NR_029616.1(MIR187):​n.98C>T variant causes a non coding transcript exon change. The variant allele was found at a frequency of 0.0134 in 492,798 control chromosomes in the GnomAD database, including 71 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 0.010 (12 hom., cov: 32)
  • Exomes 𝑓: 0.015 (59 hom.)
• Consequence: MIR187 NR_029616.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.17

Genes affected

MIR187 (HGNC:31558): (microRNA 187) 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.21).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0104 (1586/152300) while in subpopulation SAS AF= 0.0201 (97/4822). AF 95% confidence interval is 0.0169. There are 12 homozygotes in gnomad4. There are 735 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 12 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIR187	NR_029616.1	n.98C>T		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIR187	ENST00000385062.1	n.98C>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.0104 AC: 1587 AN: 152182 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.00256

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00589

Gnomad ASJ AF: 0.00864

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0203

Gnomad FIN AF: 0.00980

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0166

Gnomad OTH AF: 0.0120

GnomAD3 exomes AF: 0.0120 AC: 2226 AN: 185376 Hom.: 24 AF XY: 0.0137 AC XY: 1369 AN XY: 99760

Gnomad AFR exome AF: 0.00270

Gnomad AMR exome AF: 0.00339

Gnomad ASJ exome AF: 0.00864

Gnomad EAS exome AF: 0.000431

Gnomad SAS exome AF: 0.0230

Gnomad FIN exome AF: 0.0111

Gnomad NFE exome AF: 0.0155

Gnomad OTH exome AF: 0.0126

GnomAD4 exome AF: 0.0147 AC: 5021 AN: 340498 Hom.: 59 Cov.: 0 AF XY: 0.0158 AC XY: 3048 AN XY: 193174

Gnomad4 AFR exome AF: 0.00227

Gnomad4 AMR exome AF: 0.00351

Gnomad4 ASJ exome AF: 0.00804

Gnomad4 EAS exome AF: 0.000460

Gnomad4 SAS exome AF: 0.0235

Gnomad4 FIN exome AF: 0.0108

Gnomad4 NFE exome AF: 0.0163

Gnomad4 OTH exome AF: 0.0142

GnomAD4 genome AF: 0.0104 AC: 1586 AN: 152300 Hom.: 12 Cov.: 32 AF XY: 0.00987 AC XY: 735 AN XY: 74458

Gnomad4 AFR AF: 0.00255

Gnomad4 AMR AF: 0.00588

Gnomad4 ASJ AF: 0.00864

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0201

Gnomad4 FIN AF: 0.00980

Gnomad4 NFE AF: 0.0166

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.0131 Hom.: 12

Bravo AF: 0.00929

Asia WGS AF: 0.00606 AC: 21 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.21
CADD	Benign	22
DANN	Benign	0.95

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs41274312; hg19: chr18-33484792;