11-2172945-T-C

Variant names:

• chr11-2172945-T-C
• rs10743149
• ENST00000729706.1:n.527T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000729706.1(ENSG00000295384):​n.527T>C 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 0.881 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: ENSG00000295384 ENST00000729706.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48
• Publications: 14 publications found

Genes affected

ENSG00000295384 (HGNC:):

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000729706.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR4686	NR_039834.1		n.-118T>C		upstream_gene	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000295384	ENST00000729706.1		n.527T>C		non_coding_transcript_exon	Exon 3 of 3
	ENSG00000295384	ENST00000729705.1		n.321-1040T>C		intron	N/A
	ENSG00000295395	ENST00000729780.1		n.397-520A>G		intron	N/A

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

African (AFR) AF: 0.808 AC: 63 AN: 78

American (AMR) AF: 0.875 AC: 7 AN: 8

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 4 AN: 4

East Asian (EAS) AF: 1.00 AC: 4 AN: 4

South Asian (SAS) AF: 0.968 AC: 91 AN: 94

European-Finnish (FIN) AF: 0.800 AC: 16 AN: 20

Middle Eastern (MID) AF: 0.893 AC: 1457 AN: 1632

European-Non Finnish (NFE) AF: 0.902 AC: 240 AN: 266

Other (OTH) AF: 0.891 AC: 171 AN: 192

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

African (AFR) AF: 0.851 AC: 35345 AN: 41532

American (AMR) AF: 0.916 AC: 14020 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.881 AC: 3059 AN: 3472

East Asian (EAS) AF: 0.959 AC: 4939 AN: 5148

South Asian (SAS) AF: 0.957 AC: 4614 AN: 4822

European-Finnish (FIN) AF: 0.883 AC: 9368 AN: 10606

Middle Eastern (MID) AF: 0.901 AC: 265 AN: 294

European-Non Finnish (NFE) AF: 0.879 AC: 59773 AN: 68012

Other (OTH) AF: 0.864 AC: 1829 AN: 2116

Alfa AF: 0.879 Hom.: 30188

Bravo AF: 0.879

Asia WGS AF: 0.962 AC: 3346 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.0
DANN	Benign	0.48
PhyloP100		-1.5

Splicing

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

Other links and lift over

dbSNP: rs10743149; hg19: chr11-2194175;