rs6513496

Positions:

• chr20-60308476-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_030376.1(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 NR_030376.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.735

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

Verdict is Benign. Variant got -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	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIR646	NR_030376.1	n.3T>C		non_coding_transcript_exon_variant	1/1
MIR646HG	NR_046099.1	n.333-10445T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIR646	ENST00000385067.1	n.3T>C		non_coding_transcript_exon_variant	1/1
MIR646HG	ENST00000659856.1	n.353+127563T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42429 AN: 151766 Hom.: 6651 Cov.: 32

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

GnomAD3 exomes AF: 0.236 AC: 58464 AN: 248060 Hom.: 7589 AF XY: 0.239 AC XY: 32076 AN XY: 134474

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 SAS exome AF: 0.299

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.: 0 AF XY: 0.248 AC XY: 54139 AN XY: 218164

Gnomad4 AFR exome AF: 0.424

Gnomad4 AMR exome AF: 0.144

Gnomad4 ASJ exome AF: 0.212

Gnomad4 EAS exome AF: 0.114

Gnomad4 SAS exome AF: 0.297

Gnomad4 FIN exome AF: 0.293

Gnomad4 NFE exome AF: 0.234

Gnomad4 OTH exome AF: 0.247

GnomAD4 genome AF: 0.280 AC: 42512 AN: 151884 Hom.: 6675 Cov.: 32 AF XY: 0.276 AC XY: 20495 AN XY: 74202

Gnomad4 AFR AF: 0.426

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.210

Gnomad4 EAS AF: 0.124

Gnomad4 SAS AF: 0.302

Gnomad4 FIN AF: 0.282

Gnomad4 NFE AF: 0.232

Gnomad4 OTH AF: 0.259

Alfa AF: 0.255 Hom.: 2363

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
DANN	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6513496; hg19: chr20-58883534;