rs10840491

chr11-2173160-G-A

Variant summary

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

The 11-2173160-G-A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 154,202 control chromosomes in the GnomAD database, including 1,655 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 0.14 (1630 hom., cov: 33)
  • Exomes 𝑓: 0.14 (25 hom.)
• Consequence: MIR4686 NR_039834.1 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.574

Genes affected

MIR4686 (HGNC:41601): (microRNA 4686) 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MIR4686	NR_039834.1			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIR4686	ENST00000584128.1			downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21926 AN: 151936 Hom.: 1626 Cov.: 33

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.140

GnomAD3 exomes AF: 0.113 AC: 45 AN: 400 Hom.: 2 AF XY: 0.110 AC XY: 24 AN XY: 218

Gnomad AFR exome AF: 0.250

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.114

Gnomad OTH exome AF: 0.0833

GnomAD4 exome AF: 0.136 AC: 292 AN: 2148 Hom.: 25 Cov.: 0 AF XY: 0.134 AC XY: 144 AN XY: 1074

Gnomad4 AFR exome AF: 0.122

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.178

Gnomad4 FIN exome AF: 0.300

Gnomad4 NFE exome AF: 0.141

Gnomad4 OTH exome AF: 0.0966

GnomAD4 genome AF: 0.144 AC: 21948 AN: 152054 Hom.: 1630 Cov.: 33 AF XY: 0.146 AC XY: 10865 AN XY: 74338

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.223

Gnomad4 ASJ AF: 0.120

Gnomad4 EAS AF: 0.126

Gnomad4 SAS AF: 0.171

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.142

Alfa AF: 0.140 Hom.: 1310

Bravo AF: 0.148

Asia WGS AF: 0.146 AC: 508 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	6.8
Dann	Benign	0.61

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10840491; hg19: chr11-2194390;