chr19-53736920-G-A

Position:

• chr19-53736920-G-A

Variant summary

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

The NR_030212.1(MIR516B1):​n.76G>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 0.00939 in 532,994 control chromosomes in the GnomAD database, including 237 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 0.0073 (39 hom., cov: 32)
  • Exomes 𝑓: 0.010 (198 hom.)
• Consequence: MIR516B1 NR_030212.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.599

Genes affected

MIR516B1 (HGNC:32122): (microRNA 516b-1) 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIR516B1	NR_030212.1	n.76G>A		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIR516B1	ENST00000385211.3	n.76G>A		mature_miRNA_variant	1/1
	ENST00000710708.1	n.586-9283G>A		intron_variant, non_coding_transcript_variant
	ENST00000710696.1	n.325+321G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00726 AC: 1105 AN: 152140 Hom.: 38 Cov.: 32

Gnomad AFR AF: 0.000700

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0560

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0383

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.0150 AC: 3749 AN: 249634 Hom.: 179 AF XY: 0.0114 AC XY: 1544 AN XY: 135252

Gnomad AFR exome AF: 0.000556

Gnomad AMR exome AF: 0.0912

Gnomad ASJ exome AF: 0.000299

Gnomad EAS exome AF: 0.0321

Gnomad SAS exome AF: 0.000592

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000442

Gnomad OTH exome AF: 0.00834

GnomAD4 exome AF: 0.0102 AC: 3891 AN: 380736 Hom.: 198 Cov.: 0 AF XY: 0.00773 AC XY: 1677 AN XY: 216840

Gnomad4 AFR exome AF: 0.000478

Gnomad4 AMR exome AF: 0.0917

Gnomad4 ASJ exome AF: 0.000341

Gnomad4 EAS exome AF: 0.0390

Gnomad4 SAS exome AF: 0.000602

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000835

Gnomad4 OTH exome AF: 0.00288

GnomAD4 genome AF: 0.00730 AC: 1112 AN: 152258 Hom.: 39 Cov.: 32 AF XY: 0.00826 AC XY: 615 AN XY: 74444

Gnomad4 AFR AF: 0.000698

Gnomad4 AMR AF: 0.0563

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0382

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00162 Hom.: 3

Bravo AF: 0.0110

Asia WGS AF: 0.0200 AC: 71 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.1
DANN	Benign	0.46

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs78861479; hg19: chr19-54240174; COSMIC: COSV66046291;