rs2910164

Positions:

• chr5-160485411-C-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NR_029701.1(MIR146A):​n.60C>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 0.727 in 528,390 control chromosomes in the GnomAD database, including 141,782 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 0.70 (38097 hom., cov: 31)
  • Exomes 𝑓: 0.74 (103685 hom.)
• Consequence: MIR146A NR_029701.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.57

Genes affected

MIR3142HG (HGNC:51944): (MIR3142 host gene)

MIR146A (HGNC:31533): (microRNA 146a) 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. Some of the targets of the encoded miRNA are the transcripts for tumor necrosis factor, interleukin 1 receptor-associated kinase 1, interleukin 1-beta, TNF receptor-associated factor 6, and complement factor H. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2015]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIR146A	NR_029701.1	n.60C>G		non_coding_transcript_exon_variant	1/1
MIR3142HG	NR_132748.1	n.303C>G		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIR3142HG	ENST00000517927.1	n.286C>G		non_coding_transcript_exon_variant	2/2	1
MIR3142HG	ENST00000642173.1	n.189C>G		non_coding_transcript_exon_variant	2/2
MIR146A	ENST00000385201.1	n.60C>G		mature_miRNA_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.702 AC: 106630 AN: 151942 Hom.: 38071 Cov.: 31

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.682

Gnomad AMR AF: 0.708

Gnomad ASJ AF: 0.783

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.705

Gnomad FIN AF: 0.787

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.687

GnomAD3 exomes AF: 0.713 AC: 175623 AN: 246292 Hom.: 64108 AF XY: 0.719 AC XY: 95733 AN XY: 133108

Gnomad AFR exome AF: 0.598

Gnomad AMR exome AF: 0.694

Gnomad ASJ exome AF: 0.777

Gnomad EAS exome AF: 0.372

Gnomad SAS exome AF: 0.720

Gnomad FIN exome AF: 0.784

Gnomad NFE exome AF: 0.770

Gnomad OTH exome AF: 0.730

GnomAD4 exome AF: 0.737 AC: 277348 AN: 376330 Hom.: 103685 Cov.: 0 AF XY: 0.738 AC XY: 157630 AN XY: 213566

Gnomad4 AFR exome AF: 0.599

Gnomad4 AMR exome AF: 0.694

Gnomad4 ASJ exome AF: 0.777

Gnomad4 EAS exome AF: 0.376

Gnomad4 SAS exome AF: 0.727

Gnomad4 FIN exome AF: 0.782

Gnomad4 NFE exome AF: 0.772

Gnomad4 OTH exome AF: 0.733

GnomAD4 genome AF: 0.702 AC: 106701 AN: 152060 Hom.: 38097 Cov.: 31 AF XY: 0.702 AC XY: 52221 AN XY: 74344

Gnomad4 AFR AF: 0.607

Gnomad4 AMR AF: 0.709

Gnomad4 ASJ AF: 0.783

Gnomad4 EAS AF: 0.380

Gnomad4 SAS AF: 0.705

Gnomad4 FIN AF: 0.787

Gnomad4 NFE AF: 0.766

Gnomad4 OTH AF: 0.688

Alfa AF: 0.755 Hom.: 14093

Bravo AF: 0.691

Asia WGS AF: 0.549 AC: 1913 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	17
DANN	Benign	0.76

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2910164; hg19: chr5-159912418;