dbSNP rs6513496: MIR646:n.3T>C (chr20-60308476-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 ENST00000385067.1(MIR646):n.3T>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 0.253 in 535,282 control chromosomes in the GnomAD database, including 18,707 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 0.28 ( 6675 hom., cov: 32)

Exomes 𝑓: 0.24 ( 12032 hom. )

Consequence

MIR646
ENST00000385067.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.735

Publications

16 publications found

Variant links:

Genes affected

MIR646 (HGNC:32902): (microRNA 646) 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]

MIR646 links:

MIR646HG (HGNC:27659): (MIR646 host gene)

MIR646HG 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=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
MIR646	NR_030376.1 link	n.3T>C	non_coding_transcript_exon_variant	Exon 1 of 1
MIR646HG	NR_046099.1 link	n.333-10445T>C	intron_variant	Intron 3 of 4
MIR646	unassigned_transcript_3468	n.-58T>C	upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
MIR646	ENST00000385067.1 link	n.3T>C	non_coding_transcript_exon_variant	Exon 1 of 1	6
MIR646HG	ENST00000421257.1 link	n.36-4834T>C	intron_variant	Intron 1 of 2	3
MIR646HG	ENST00000432910.5 link	n.333-10445T>C	intron_variant	Intron 3 of 4	2

Frequencies

GnomAD3 genomes

AF:

0.280

AC:

42429

AN:

151766

Hom.:

6651

Cov.:

show subpopulations

Gnomad AFR

AF:

0.425

Gnomad AMI

AF:

0.100

Gnomad AMR

AF:

0.174

Gnomad ASJ

AF:

0.210

Gnomad EAS

AF:

0.124

Gnomad SAS

AF:

0.301

Gnomad FIN

AF:

0.282

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.232

Gnomad OTH

AF:

0.254

GnomAD2 exomes

AF:

0.236

AC:

58464

AN:

248060

AF XY:

0.239

show subpopulations

Gnomad AFR exome

AF:

0.425

Gnomad AMR exome

AF:

0.144

Gnomad ASJ exome

AF:

0.214

Gnomad EAS exome

AF:

0.109

Gnomad FIN exome

AF:

0.288

Gnomad NFE exome

AF:

0.232

Gnomad OTH exome

AF:

0.241

GnomAD4 exome

AF:

0.242

AC:

92951

AN:

383398

Hom.:

12032

Cov.:

AF XY:

0.248

AC XY:

54139

AN XY:

218164

show subpopulations

African (AFR)

AF:

0.424

AC:

4467

AN:

10536

American (AMR)

AF:

0.144

AC:

5225

AN:

36308

Ashkenazi Jewish (ASJ)

AF:

0.212

AC:

2493

AN:

11774

East Asian (EAS)

AF:

0.114

AC:

1524

AN:

13330

South Asian (SAS)

AF:

0.297

AC:

19853

AN:

66742

European-Finnish (FIN)

AF:

0.293

AC:

9493

AN:

32444

Middle Eastern (MID)

AF:

0.269

AC:

769

AN:

2858

European-Non Finnish (NFE)

AF:

0.234

AC:

44987

AN:

192626

Other (OTH)

AF:

0.247

AC:

4140

AN:

16780

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

3733

7467

11200

14934

18667

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

398

796

1194

1592

1990

<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:

0.280

AC:

42512

AN:

151884

Hom.:

6675

Cov.:

AF XY:

0.276

AC XY:

20495

AN XY:

74202

show subpopulations

African (AFR)

AF:

0.426

AC:

17612

AN:

41390

American (AMR)

AF:

0.173

AC:

2649

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.210

AC:

728

AN:

3470

East Asian (EAS)

AF:

0.124

AC:

636

AN:

5130

South Asian (SAS)

AF:

0.302

AC:

1456

AN:

4818

European-Finnish (FIN)

AF:

0.282

AC:

2976

AN:

10550

Middle Eastern (MID)

AF:

0.221

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.232

AC:

15753

AN:

67944

Other (OTH)

AF:

0.259

AC:

546

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1507

3014

4522

6029

7536

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

428

856

1284

1712

2140

<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:

0.257

Hom.:

2430

Bravo

AF:

0.274

Asia WGS

AF:

0.241

AC:

840

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.92

(source)

DANN

Benign

0.75

PhyloP100

-0.73

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