rs16884450

Variant names:

• chr6-91521500-G-T
• rs16884450
• ENST00000577473.1:n.-160G>T

Variant summary

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

The NR_039786.1(MIR4643):​n.-160G>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,146 control chromosomes in the GnomAD database, including 1,266 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 0.11 (1266 hom., cov: 32)
• Consequence: MIR4643 NR_039786.1 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.477

Genes affected

MIR4643 (HGNC:41814): (microRNA 4643) 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIR4643	NR_039786.1	n.-160G>T		upstream_gene_variant
MIR4643	unassigned_transcript_1156	n.-209G>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIR4643	ENST00000577473.1	n.-160G>T		upstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17248 AN: 152026 Hom.: 1259 Cov.: 32

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.0648

Gnomad ASJ AF: 0.0369

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.0894

Gnomad FIN AF: 0.0632

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0775

Gnomad OTH AF: 0.107

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.114 AC: 17284 AN: 152146 Hom.: 1266 Cov.: 32 AF XY: 0.113 AC XY: 8409 AN XY: 74384

Gnomad4 AFR AF: 0.206

Gnomad4 AMR AF: 0.0648

Gnomad4 ASJ AF: 0.0369

Gnomad4 EAS AF: 0.181

Gnomad4 SAS AF: 0.0886

Gnomad4 FIN AF: 0.0632

Gnomad4 NFE AF: 0.0775

Gnomad4 OTH AF: 0.108

Alfa AF: 0.0870 Hom.: 171

Bravo AF: 0.116

Asia WGS AF: 0.131 AC: 455 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.60
DANN	Benign	0.53

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16884450; hg19: chr6-92231218; COSMIC: COSV73972760;