dbSNP rs75330474: MIR323B:n.34C>T (chr14-101056252-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000699461.1(MEG9):n.381+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0157 in 533,574 control chromosomes in the GnomAD database, including 203 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 0.025 ( 108 hom., cov: 33)

Exomes 𝑓: 0.012 ( 95 hom. )

Consequence

MEG9
ENST00000699461.1 splice_region, intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.47

Publications

15 publications found

Variant links:

Genes affected

MIR323B (HGNC:38349): (microRNA 323b) 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]

MIR323B links:

MEG9 (HGNC:43874): (maternally expressed 9)

MEG9 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=-0.6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0683 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000699461.1. 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
	MIR323B	NR_036133.1		n.34C>T		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
MIR323B	ENST00000385269.2	TSL:6	n.34C>T	non_coding_transcript_exon	Exon 1 of 1
MEG9	ENST00000699461.1		n.381+8C>T	splice_region intron	N/A
MEG9	ENST00000699460.1		n.*8C>T	downstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.0249

AC:

3788

AN:

152142

Hom.:

108

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0705

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00622

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.0528

Gnomad SAS

AF:

0.0292

Gnomad FIN

AF:

0.00687

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00347

Gnomad OTH

AF:

0.0196

GnomAD2 exomes

AF:

0.0150

AC:

3765

AN:

250602

AF XY:

0.0145

show subpopulations

Gnomad AFR exome

AF:

0.0704

Gnomad AMR exome

AF:

0.00402

Gnomad ASJ exome

AF:

0.00269

Gnomad EAS exome

AF:

0.0519

Gnomad FIN exome

AF:

0.00599

Gnomad NFE exome

AF:

0.00407

Gnomad OTH exome

AF:

0.0114

GnomAD4 exome

AF:

0.0120

AC:

4588

AN:

381314

Hom.:

Cov.:

AF XY:

0.0130

AC XY:

2816

AN XY:

217154

show subpopulations

African (AFR)

AF:

0.0705

AC:

738

AN:

10466

American (AMR)

AF:

0.00386

AC:

140

AN:

36294

Ashkenazi Jewish (ASJ)

AF:

0.00272

AC:

AN:

11744

East Asian (EAS)

AF:

0.0482

AC:

634

AN:

13160

South Asian (SAS)

AF:

0.0276

AC:

1843

AN:

66680

European-Finnish (FIN)

AF:

0.00579

AC:

187

AN:

32318

Middle Eastern (MID)

AF:

0.00453

AC:

AN:

1986

European-Non Finnish (NFE)

AF:

0.00432

AC:

829

AN:

192040

Other (OTH)

AF:

0.0106

AC:

176

AN:

16626

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

204

409

613

818

1022

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

138

184

230

<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:

0.0249

AC:

3792

AN:

152260

Hom.:

108

Cov.:

AF XY:

0.0240

AC XY:

1785

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.0704

AC:

2925

AN:

41528

American (AMR)

AF:

0.00628

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3470

East Asian (EAS)

AF:

0.0527

AC:

273

AN:

5178

South Asian (SAS)

AF:

0.0290

AC:

140

AN:

4824

European-Finnish (FIN)

AF:

0.00687

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00347

AC:

236

AN:

68024

Other (OTH)

AF:

0.0194

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

184

369

553

738

922

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

168

210

<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:

0.0123

Hom.:

Bravo

AF:

0.0269

Asia WGS

AF:

0.0540

AC:

188

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

8.2

(source)

DANN

Benign

0.93

PhyloP100

-1.5

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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