rs6513496

Variant names:

• chr20-60308476-T-C
• rs6513496
• ENST00000385067.1:n.3T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.42 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.3T>C		non_coding_transcript_exon	Exon 1 of 1
	MIR646HG	NR_046099.1		n.333-10445T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR646	ENST00000385067.1	TSL:6	n.3T>C		non_coding_transcript_exon	Exon 1 of 1
	MIR646HG	ENST00000421257.1	TSL:3	n.36-4834T>C		intron	N/A
	MIR646HG	ENST00000432910.5	TSL:2	n.333-10445T>C		intron	N/A

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

GnomAD2 exomes AF: 0.236 AC: 58464 AN: 248060 AF XY: 0.239

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 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

African (AFR) AF: 0.424 AC: 4467 AN: 10536

American (AMR) AF: 0.144 AC: 5225 AN: 36308

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 2493 AN: 11774

East Asian (EAS) AF: 0.114 AC: 1524 AN: 13330

South Asian (SAS) AF: 0.297 AC: 19853 AN: 66742

European-Finnish (FIN) AF: 0.293 AC: 9493 AN: 32444

Middle Eastern (MID) AF: 0.269 AC: 769 AN: 2858

European-Non Finnish (NFE) AF: 0.234 AC: 44987 AN: 192626

Other (OTH) AF: 0.247 AC: 4140 AN: 16780

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

African (AFR) AF: 0.426 AC: 17612 AN: 41390

American (AMR) AF: 0.173 AC: 2649 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 728 AN: 3470

East Asian (EAS) AF: 0.124 AC: 636 AN: 5130

South Asian (SAS) AF: 0.302 AC: 1456 AN: 4818

European-Finnish (FIN) AF: 0.282 AC: 2976 AN: 10550

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.232 AC: 15753 AN: 67944

Other (OTH) AF: 0.259 AC: 546 AN: 2106

Alfa AF: 0.257 Hom.: 2430

Bravo AF: 0.274

Asia WGS AF: 0.241 AC: 840 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.92
DANN	Benign	0.75
PhyloP100		-0.73

Splicing

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

Other links and lift over

dbSNP: rs6513496; hg19: chr20-58883534;