rs61388742

Positions:

• chr8-1817259-T-C

Variant summary

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

The NR_030326.1(MIR596):​n.29T>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 0.085 in 516,166 control chromosomes in the GnomAD database, including 2,251 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 0.094 (689 hom., cov: 33)
  • Exomes 𝑓: 0.081 (1562 hom.)
• Consequence: MIR596 NR_030326.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0480

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIR596	NR_030326.1	n.29T>C		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIR596	ENST00000385091.1	n.29T>C		mature_miRNA_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.0944 AC: 14367 AN: 152144 Hom.: 689 Cov.: 33

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0782

Gnomad ASJ AF: 0.0942

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0130

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.102

GnomAD3 exomes AF: 0.0813 AC: 19664 AN: 242000 Hom.: 992 AF XY: 0.0794 AC XY: 10419 AN XY: 131280

Gnomad AFR exome AF: 0.104

Gnomad AMR exome AF: 0.0539

Gnomad ASJ exome AF: 0.0969

Gnomad EAS exome AF: 0.000170

Gnomad SAS exome AF: 0.0144

Gnomad FIN exome AF: 0.106

Gnomad NFE exome AF: 0.109

Gnomad OTH exome AF: 0.0967

GnomAD4 exome AF: 0.0811 AC: 29522 AN: 363904 Hom.: 1562 Cov.: 0 AF XY: 0.0761 AC XY: 15654 AN XY: 205804

Gnomad4 AFR exome AF: 0.0953

Gnomad4 AMR exome AF: 0.0544

Gnomad4 ASJ exome AF: 0.0966

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0153

Gnomad4 FIN exome AF: 0.106

Gnomad4 NFE exome AF: 0.108

Gnomad4 OTH exome AF: 0.0901

GnomAD4 genome AF: 0.0944 AC: 14368 AN: 152262 Hom.: 689 Cov.: 33 AF XY: 0.0932 AC XY: 6941 AN XY: 74462

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.0781

Gnomad4 ASJ AF: 0.0942

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0133

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.100

Alfa AF: 0.102 Hom.: 346

Bravo AF: 0.0929

Asia WGS AF: 0.0180 AC: 62 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.4
DANN	Benign	0.24

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs61388742; hg19: chr8-1765425;