rs10670323

Variant names:

• chr19-53725488-G-GAAAGA
• rs10670323
• ENST00000385190.1:n.50_54dupAGAAA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000385190.1(MIR516B2):​n.50_54dupAGAAA 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 0.151 in 152,026 control chromosomes in the GnomAD database, including 2,317 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.15 (2317 hom., cov: 29)
  • Exomes 𝑓: 0.11 (2616 hom.)
  • Failed GnomAD Quality Control
• Consequence: MIR516B2 ENST00000385190.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347
• Publications: 6 publications found

Genes affected

MIR516B2 (HGNC:32117): (microRNA 516b-2) 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]

ENSG00000269842 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIR516B2	NR_030207.1	n.50_54dupAGAAA		non_coding_transcript_exon_variant	Exon 1 of 1
MIR516B2	unassigned_transcript_3368	n.-9_-8insAAAGA		upstream_gene_variant
MIR516B2	unassigned_transcript_3367	n.*10_*11insAAAGA		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIR516B2	ENST00000385190.1	n.50_54dupAGAAA		non_coding_transcript_exon_variant	Exon 1 of 1	6
ENSG00000269842	ENST00000710708.1	n.585+12390_585+12394dupAGAAA		intron_variant	Intron 4 of 9

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22932 AN: 151908 Hom.: 2309 Cov.: 29

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.0727

Gnomad ASJ AF: 0.0723

Gnomad EAS AF: 0.0644

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.132

GnomAD2 exomes AF: 0.0665 AC: 15644 AN: 235408 AF XY: 0.0640

Gnomad AFR exome AF: 0.202

Gnomad AMR exome AF: 0.0320

Gnomad ASJ exome AF: 0.0346

Gnomad EAS exome AF: 0.0468

Gnomad FIN exome AF: 0.126

Gnomad NFE exome AF: 0.0576

Gnomad OTH exome AF: 0.0590

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.107 AC: 39550 AN: 369680 Hom.: 2616 Cov.: 0 AF XY: 0.107 AC XY: 22384 AN XY: 209112

African (AFR) AF: 0.296 AC: 3053 AN: 10310

American (AMR) AF: 0.0511 AC: 1838 AN: 35996

Ashkenazi Jewish (ASJ) AF: 0.0681 AC: 784 AN: 11510

East Asian (EAS) AF: 0.0631 AC: 806 AN: 12764

South Asian (SAS) AF: 0.112 AC: 7253 AN: 64738

European-Finnish (FIN) AF: 0.165 AC: 5285 AN: 31970

Middle Eastern (MID) AF: 0.128 AC: 359 AN: 2810

European-Non Finnish (NFE) AF: 0.101 AC: 18453 AN: 183428

Other (OTH) AF: 0.106 AC: 1719 AN: 16154

GnomAD4 genome AF: 0.151 AC: 22982 AN: 152026 Hom.: 2317 Cov.: 29 AF XY: 0.151 AC XY: 11195 AN XY: 74328

African (AFR) AF: 0.287 AC: 11865 AN: 41408

American (AMR) AF: 0.0725 AC: 1107 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0723 AC: 251 AN: 3472

East Asian (EAS) AF: 0.0641 AC: 332 AN: 5176

South Asian (SAS) AF: 0.104 AC: 502 AN: 4820

European-Finnish (FIN) AF: 0.160 AC: 1695 AN: 10584

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.100 AC: 6821 AN: 67976

Other (OTH) AF: 0.131 AC: 277 AN: 2114

Alfa AF: 0.116 Hom.: 240

Bravo AF: 0.150

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.35

Splicing

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

Other links and lift over

dbSNP: rs10670323; hg19: chr19-54228742; COSMIC: COSV66082915;