rs16884450

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000577473.1(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 ENST00000577473.1 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.477
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000577473.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR4643	NR_039786.1		n.-160G>T		upstream_gene	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR4643	ENST00000577473.1	TSL:6	n.-160G>T		upstream_gene	N/A

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

African (AFR) AF: 0.206 AC: 8566 AN: 41498

American (AMR) AF: 0.0648 AC: 989 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0369 AC: 128 AN: 3470

East Asian (EAS) AF: 0.181 AC: 933 AN: 5150

South Asian (SAS) AF: 0.0886 AC: 428 AN: 4828

European-Finnish (FIN) AF: 0.0632 AC: 671 AN: 10610

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0775 AC: 5269 AN: 67996

Other (OTH) AF: 0.108 AC: 228 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.60
DANN	Benign	0.53
PhyloP100		-0.48

Splicing

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

Other links and lift over

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