rs56013413

chr19-53742534-G-A

Variant summary

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

The NR_030215.1(MIR520H):n.23G>A 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 0.05 in 532,498 control chromosomes in the GnomAD database, including 1,489 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 0.084 (1047 hom., cov: 32)
  • Exomes 𝑓: 0.037 (442 hom.)
• Consequence: MIR520H NR_030215.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365

Genes affected

MIR520H (HGNC:32125): (microRNA 520h) 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]

(HGNC:):

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 = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MIR520H	NR_030215.1	n.23G>A		non_coding_transcript_exon_variant	1/1
LOC124904765	XR_007067334.1	n.373+267G>A		intron_variant, non_coding_transcript_variant
LOC124904765	XR_007067333.1	n.281+267G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIR520H	ENST00000385126.1	n.23G>A		non_coding_transcript_exon_variant	1/1
	ENST00000710708.1	n.586-3669G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0834 AC: 12691 AN: 152084 Hom.: 1044 Cov.: 32

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.00769

Gnomad AMR AF: 0.0434

Gnomad ASJ AF: 0.0291

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0240

Gnomad FIN AF: 0.0452

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0327

Gnomad OTH AF: 0.0684

GnomAD3 exomes AF: 0.0424 AC: 10479 AN: 247214 Hom.: 541 AF XY: 0.0391 AC XY: 5229 AN XY: 133746

Gnomad AFR exome AF: 0.224

Gnomad AMR exome AF: 0.0241

Gnomad ASJ exome AF: 0.0256

Gnomad EAS exome AF: 0.000443

Gnomad SAS exome AF: 0.0243

Gnomad FIN exome AF: 0.0461

Gnomad NFE exome AF: 0.0347

Gnomad OTH exome AF: 0.0324

GnomAD4 exome AF: 0.0365 AC: 13887 AN: 380296 Hom.: 442 Cov.: 0 AF XY: 0.0349 AC XY: 7548 AN XY: 216540

Gnomad4 AFR exome AF: 0.221

Gnomad4 AMR exome AF: 0.0235

Gnomad4 ASJ exome AF: 0.0243

Gnomad4 EAS exome AF: 0.000228

Gnomad4 SAS exome AF: 0.0242

Gnomad4 FIN exome AF: 0.0433

Gnomad4 NFE exome AF: 0.0349

Gnomad4 OTH exome AF: 0.0402

GnomAD4 genome AF: 0.0836 AC: 12717 AN: 152202 Hom.: 1047 Cov.: 32 AF XY: 0.0807 AC XY: 6004 AN XY: 74426

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.0434

Gnomad4 ASJ AF: 0.0291

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0240

Gnomad4 FIN AF: 0.0452

Gnomad4 NFE AF: 0.0327

Gnomad4 OTH AF: 0.0676

Alfa AF: 0.0550 Hom.: 246

Bravo AF: 0.0892

Asia WGS AF: 0.0260 AC: 91 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	2.3
Dann	Benign	0.38

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs56013413; hg19: chr19-54245788;