Variant 20-60308547-T-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NR_030376.1(MIR646):n.74T>G 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 0.123 in 537,602 control chromosomes in the GnomAD database, including 6,402 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 0.17 ( 3629 hom., cov: 32)

Exomes 𝑓: 0.10 ( 2773 hom. )

Consequence

MIR646
NR_030376.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.355

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:

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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=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MIR646	NR_030376.1 linkuse as main transcript	n.74T>G		non_coding_transcript_exon_variant	1/1
MIR646HG	NR_046099.1 linkuse as main transcript	n.333-10374T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIR646	ENST00000385067.1 linkuse as main transcript	n.74T>G		mature_miRNA_variant	1/1
MIR646HG	ENST00000659856.1 linkuse as main transcript	n.353+127634T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.170

AC:

25796

AN:

151922

Hom.:

3608

Cov.:

show subpopulations

Gnomad AFR

AF:

0.388

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0911

Gnomad ASJ

AF:

0.0550

Gnomad EAS

AF:

0.110

Gnomad SAS

AF:

0.149

Gnomad FIN

AF:

0.122

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.0777

Gnomad OTH

AF:

0.143

GnomAD3 exomes

AF:

0.112

AC:

27823

AN:

248218

Hom.:

2350

AF XY:

0.109

AC XY:

14616

AN XY:

134598

show subpopulations

Gnomad AFR exome

AF:

0.390

Gnomad AMR exome

AF:

0.0870

Gnomad ASJ exome

AF:

0.0539

Gnomad EAS exome

AF:

0.0982

Gnomad SAS exome

AF:

0.144

Gnomad FIN exome

AF:

0.116

Gnomad NFE exome

AF:

0.0782

Gnomad OTH exome

AF:

0.0981

GnomAD4 exome

AF:

0.104

AC:

40089

AN:

385562

Hom.:

2773

Cov.:

AF XY:

0.105

AC XY:

23127

AN XY:

219362

show subpopulations

Gnomad4 AFR exome

AF:

0.388

Gnomad4 AMR exome

AF:

0.0862

Gnomad4 ASJ exome

AF:

0.0568

Gnomad4 EAS exome

AF:

0.104

Gnomad4 SAS exome

AF:

0.143

Gnomad4 FIN exome

AF:

0.116

Gnomad4 NFE exome

AF:

0.0788

Gnomad4 OTH exome

AF:

0.108

GnomAD4 genome

AF:

0.170

AC:

25858

AN:

152040

Hom.:

3629

Cov.:

AF XY:

0.169

AC XY:

12546

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.388

Gnomad4 AMR

AF:

0.0910

Gnomad4 ASJ

AF:

0.0550

Gnomad4 EAS

AF:

0.109

Gnomad4 SAS

AF:

0.149

Gnomad4 FIN

AF:

0.122

Gnomad4 NFE

AF:

0.0777

Gnomad4 OTH

AF:

0.146

Alfa

AF:

0.0974

Hom.:

638

Bravo

AF:

0.175

Asia WGS

AF:

0.155

AC:

539

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

Cadd

Benign

1.6

Dann

Benign

0.77

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