rs6980781

Positions:

• chr8-1817205-G-A
• chr8-1817205-G-C

Variant summary

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

The 8-1817205-G-A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 488,014 control chromosomes in the GnomAD database, including 6,551 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 0.16 (2307 hom., cov: 33)
  • Exomes 𝑓: 0.14 (4244 hom.)
• Consequence: MIR596 NR_030326.1 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.510

Genes affected

MIR596 (HGNC:32852): (microRNA 596) 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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MIR596	NR_030326.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIR596	ENST00000385091.1			upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.158 AC: 23972 AN: 152062 Hom.: 2302 Cov.: 33

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.0973

Gnomad ASJ AF: 0.0623

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.133

GnomAD3 exomes AF: 0.136 AC: 30636 AN: 224744 Hom.: 2609 AF XY: 0.141 AC XY: 17238 AN XY: 122212

Gnomad AFR exome AF: 0.258

Gnomad AMR exome AF: 0.0638

Gnomad ASJ exome AF: 0.0681

Gnomad EAS exome AF: 0.124

Gnomad SAS exome AF: 0.261

Gnomad FIN exome AF: 0.183

Gnomad NFE exome AF: 0.107

Gnomad OTH exome AF: 0.124

GnomAD4 exome AF: 0.140 AC: 47130 AN: 335834 Hom.: 4244 Cov.: 0 AF XY: 0.151 AC XY: 28434 AN XY: 188292

Gnomad4 AFR exome AF: 0.263

Gnomad4 AMR exome AF: 0.0641

Gnomad4 ASJ exome AF: 0.0653

Gnomad4 EAS exome AF: 0.122

Gnomad4 SAS exome AF: 0.253

Gnomad4 FIN exome AF: 0.180

Gnomad4 NFE exome AF: 0.105

Gnomad4 OTH exome AF: 0.126

GnomAD4 genome AF: 0.158 AC: 24012 AN: 152180 Hom.: 2307 Cov.: 33 AF XY: 0.163 AC XY: 12102 AN XY: 74410

Gnomad4 AFR AF: 0.262

Gnomad4 AMR AF: 0.0970

Gnomad4 ASJ AF: 0.0623

Gnomad4 EAS AF: 0.131

Gnomad4 SAS AF: 0.254

Gnomad4 FIN AF: 0.184

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.137

Alfa AF: 0.110 Hom.: 1623

Bravo AF: 0.150

Asia WGS AF: 0.218 AC: 758 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.3
DANN	Benign	0.67

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6980781; hg19: chr8-1765371; COSMIC: COSV66089055;