Genetic Variant ENST00000584128.1:n.-118T>C (chr11-2172945-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000584128.1(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
ENST00000584128.1 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.48

Publications

14 publications found

Variant links:

Genes affected

ENSG00000295384 (HGNC:):

ENSG00000295384 links:

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]

MIR4686 links:

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ACMG classification

Classification was made for transcript

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: ENST00000584128.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

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

Ensembl Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank
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.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.808

AC:

AN:

American (AMR)

AF:

0.875

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AF:

0.968

AC:

AN:

European-Finnish (FIN)

AF:

0.800

AC:

AN:

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.881

AC:

134092

AN:

152216

Hom.:

59060

Cov.:

AF XY:

0.884

AC XY:

65734

AN XY:

74400

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

824

1648

2473

3297

4121

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

902

1804

2706

3608

4510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.48

PhyloP100

-1.5

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over