chr11-2172945-T-C

Variant names:

• chr11-2172945-T-C
• rs10743149
• ENST00000584128.1:n.-118T>C

Variant summary

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

The NR_039834.1(MIR4686):​n.-118T>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.881 in 152,216 control chromosomes in the GnomAD database, including 59,060 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 0.88 (59060 hom., cov: 33)
  • Exomes 𝑓: 0.89 (917 hom.)
  • Failed GnomAD Quality Control
• Consequence: MIR4686 NR_039834.1 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.937 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIR4686	NR_039834.1	n.-118T>C		upstream_gene_variant
MIR4686	unassigned_transcript_1824	n.-127T>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIR4686	ENST00000584128.1	n.-118T>C		upstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.881 AC: 133999 AN: 152098 Hom.: 59021 Cov.: 33

Gnomad AFR AF: 0.851

Gnomad AMI AF: 0.965

Gnomad AMR AF: 0.916

Gnomad ASJ AF: 0.881

Gnomad EAS AF: 0.959

Gnomad SAS AF: 0.957

Gnomad FIN AF: 0.883

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.879

Gnomad OTH AF: 0.863

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.893 AC: 2053 AN: 2298 Hom.: 917 AF XY: 0.888 AC XY: 1032 AN XY: 1162

Gnomad4 AFR exome AF: 0.808

Gnomad4 AMR exome AF: 0.875

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.968

Gnomad4 FIN exome AF: 0.800

Gnomad4 NFE exome AF: 0.902

Gnomad4 OTH exome AF: 0.891

GnomAD4 genome AF: 0.881 AC: 134092 AN: 152216 Hom.: 59060 Cov.: 33 AF XY: 0.884 AC XY: 65734 AN XY: 74400

Gnomad4 AFR AF: 0.851

Gnomad4 AMR AF: 0.916

Gnomad4 ASJ AF: 0.881

Gnomad4 EAS AF: 0.959

Gnomad4 SAS AF: 0.957

Gnomad4 FIN AF: 0.883

Gnomad4 NFE AF: 0.879

Gnomad4 OTH AF: 0.864

Alfa AF: 0.879 Hom.: 18663

Bravo AF: 0.879

Asia WGS AF: 0.962 AC: 3346 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.0
DANN	Benign	0.48

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10743149; hg19: chr11-2194175;