20-60308547-T-G

Variant names:

• chr20-60308547-T-G
• rs6513497
• ENST00000385067.1:n.74T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.355
• Publications: 22 publications found

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]

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

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NR_030376.1. 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
	MIR646	NR_030376.1		n.74T>G		non_coding_transcript_exon	Exon 1 of 1
	MIR646HG	NR_046099.1		n.333-10374T>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR646	ENST00000385067.1	TSL:6	n.74T>G		non_coding_transcript_exon	Exon 1 of 1
	MIR646HG	ENST00000421257.1	TSL:3	n.36-4763T>G		intron	N/A
	MIR646HG	ENST00000432910.5	TSL:2	n.333-10374T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25796 AN: 151922 Hom.: 3608 Cov.: 32

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

GnomAD2 exomes AF: 0.112 AC: 27823 AN: 248218 AF XY: 0.109

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 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.: 0 AF XY: 0.105 AC XY: 23127 AN XY: 219362

African (AFR) AF: 0.388 AC: 4100 AN: 10570

American (AMR) AF: 0.0862 AC: 3133 AN: 36342

Ashkenazi Jewish (ASJ) AF: 0.0568 AC: 672 AN: 11838

East Asian (EAS) AF: 0.104 AC: 1408 AN: 13530

South Asian (SAS) AF: 0.143 AC: 9553 AN: 66766

European-Finnish (FIN) AF: 0.116 AC: 3790 AN: 32676

Middle Eastern (MID) AF: 0.112 AC: 321 AN: 2864

European-Non Finnish (NFE) AF: 0.0788 AC: 15289 AN: 194092

Other (OTH) AF: 0.108 AC: 1823 AN: 16884

GnomAD4 genome AF: 0.170 AC: 25858 AN: 152040 Hom.: 3629 Cov.: 32 AF XY: 0.169 AC XY: 12546 AN XY: 74328

African (AFR) AF: 0.388 AC: 16073 AN: 41392

American (AMR) AF: 0.0910 AC: 1392 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0550 AC: 191 AN: 3470

East Asian (EAS) AF: 0.109 AC: 564 AN: 5156

South Asian (SAS) AF: 0.149 AC: 716 AN: 4814

European-Finnish (FIN) AF: 0.122 AC: 1292 AN: 10588

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0777 AC: 5285 AN: 68012

Other (OTH) AF: 0.146 AC: 309 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.6
DANN	Benign	0.77
PhyloP100		-0.35

Splicing

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

Other links and lift over

dbSNP: rs6513497; hg19: chr20-58883605;