Variant rs75330474 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000699461.1(MEG9):n.381+8C>T variant causes a splice region, intron, non coding transcript 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, non_coding_transcript

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.47

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MIR323B	NR_036133.1 linkuse as main transcript	n.34C>T		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons
MIR323B	ENST00000385269.2 linkuse as main transcript	n.34C>T	mature_miRNA_variant	1/1
MEG9	ENST00000699461.1 linkuse as main transcript	n.381+8C>T	splice_region_variant, intron_variant, non_coding_transcript_variant
MEG9	ENST00000699460.1 linkuse as main transcript		downstream_gene_variant

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

GnomAD3 exomes

AF:

0.0150

AC:

3765

AN:

250602

Hom.:

AF XY:

0.0145

AC XY:

1961

AN XY:

135668

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 SAS exome

AF:

0.0277

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

Gnomad4 AFR exome

AF:

0.0705

Gnomad4 AMR exome

AF:

0.00386

Gnomad4 ASJ exome

AF:

0.00272

Gnomad4 EAS exome

AF:

0.0482

Gnomad4 SAS exome

AF:

0.0276

Gnomad4 FIN exome

AF:

0.00579

Gnomad4 NFE exome

AF:

0.00432

Gnomad4 OTH exome

AF:

0.0106

GnomAD4 genome

AF:

0.0249

AC:

3792

AN:

152260

Hom.:

108

Cov.:

AF XY:

0.0240

AC XY:

1785

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0704

Gnomad4 AMR

AF:

0.00628

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.0527

Gnomad4 SAS

AF:

0.0290

Gnomad4 FIN

AF:

0.00687

Gnomad4 NFE

AF:

0.00347

Gnomad4 OTH

AF:

0.0194

Alfa

AF:

0.0120

Hom.:

Bravo

AF:

0.0269

Asia WGS

AF:

0.0540

AC:

188

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

8.2

DANN

Benign

0.93

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over