11-2173160-G-A

Variant names:

• chr11-2173160-G-A
• rs10840491
• ENST00000729705.1:n.321-825G>A

Variant summary

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

The ENST00000729705.1(ENSG00000295384):​n.321-825G>A variant causes a intron 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: ENSG00000295384 ENST00000729705.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.574
• Publications: 19 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=-0.89).
• 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 rank	MANE	Protein	UniProt
MIR4686	NR_039834.1	n.*22G>A		downstream_gene_variant
MIR4686	unassigned_transcript_1824	n.*66G>A		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000295384	ENST00000729705.1	n.321-825G>A		intron_variant	Intron 2 of 2
ENSG00000295395	ENST00000729780.1	n.397-735C>T		intron_variant	Intron 2 of 2
ENSG00000295395	ENST00000729781.1	n.421-735C>T		intron_variant	Intron 2 of 2

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

GnomAD2 exomes AF: 0.113 AC: 45 AN: 400 AF XY: 0.110

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

African (AFR) AF: 0.122 AC: 9 AN: 74

American (AMR) AF: 0.00 AC: 0 AN: 4

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AF: 0.178 AC: 16 AN: 90

European-Finnish (FIN) AF: 0.300 AC: 3 AN: 10

Middle Eastern (MID) AF: 0.138 AC: 216 AN: 1568

European-Non Finnish (NFE) AF: 0.141 AC: 31 AN: 220

Other (OTH) AF: 0.0966 AC: 17 AN: 176

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

African (AFR) AF: 0.134 AC: 5568 AN: 41438

American (AMR) AF: 0.223 AC: 3405 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 416 AN: 3472

East Asian (EAS) AF: 0.126 AC: 651 AN: 5160

South Asian (SAS) AF: 0.171 AC: 825 AN: 4820

European-Finnish (FIN) AF: 0.139 AC: 1470 AN: 10596

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.135 AC: 9186 AN: 67964

Other (OTH) AF: 0.142 AC: 300 AN: 2110

Alfa AF: 0.139 Hom.: 3689

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
PhyloP100		-0.57

Splicing

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

Other links and lift over

dbSNP: rs10840491; hg19: chr11-2194390;