dbSNP rs10840491: ENSG00000295384:n.321-825G>A (chr11-2173160-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.574

Publications

19 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:

Genome browser will be placed here

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=-0.89).

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 link	n.*22G>A		downstream_gene_variant
MIR4686	unassigned_transcript_1824	n.*66G>A		downstream_gene_variant

Ensembl

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

Frequencies

GnomAD3 genomes

AF:

0.144

AC:

21926

AN:

151936

Hom.:

1626

Cov.:

show subpopulations

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:

AN:

400

AF XY:

0.110

show subpopulations

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.:

Cov.:

AF XY:

0.134

AC XY:

144

AN XY:

1074

show subpopulations

African (AFR)

AF:

0.122

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.178

AC:

AN:

European-Finnish (FIN)

AF:

0.300

AC:

AN:

Middle Eastern (MID)

AF:

0.138

AC:

216

AN:

1568

European-Non Finnish (NFE)

AF:

0.141

AC:

AN:

220

Other (OTH)

AF:

0.0966

AC:

AN:

176

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

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

<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:

0.144

AC:

21948

AN:

152054

Hom.:

1630

Cov.:

AF XY:

0.146

AC XY:

10865

AN XY:

74338

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.135

AC:

9186

AN:

67964

Other (OTH)

AF:

0.142

AC:

300

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

979

1959

2938

3918

4897

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

248

496

744

992

1240

<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:

0.139

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

(source)

DANN

Benign

0.61

PhyloP100

-0.57

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over