11-81890842-A-G

Variant names:

• chr11-81890842-A-G
• rs11603185
• ENST00000500502.5:n.941-8546T>C

Variant summary

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

The ENST00000500502.5(MIR4300HG):​n.941-8546T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0432 in 154,458 control chromosomes in the GnomAD database, including 158 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 0.043 (155 hom., cov: 32)
  • Exomes 𝑓: 0.051 (3 hom.)
• Consequence: MIR4300HG ENST00000500502.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.209
• Publications: 2 publications found

Genes affected

MIR4300HG (HGNC:52003): (MIR4300 host gene)

MIR4300 (HGNC:38184): (microRNA 4300) 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=-0.91).
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.051 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000500502.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR4300HG	NR_120571.1		n.941-8546T>C		intron	N/A
	MIR4300	NR_036186.1		n.-6T>C		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR4300HG	ENST00000500502.5	TSL:1	n.941-8546T>C		intron	N/A
	MIR4300HG	ENST00000530896.6	TSL:3	n.473-8546T>C		intron	N/A
	MIR4300HG	ENST00000653173.1		n.419-65911T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0431 AC: 6535 AN: 151724 Hom.: 156 Cov.: 32

Gnomad AFR AF: 0.0466

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.0380

Gnomad ASJ AF: 0.0586

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0176

Gnomad FIN AF: 0.0215

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0481

Gnomad OTH AF: 0.0374

GnomAD2 exomes AF: 0.0508 AC: 324 AN: 6382 AF XY: 0.0536

Gnomad AFR exome AF: 0.0455

Gnomad AMR exome AF: 0.0593

Gnomad ASJ exome AF: 0.0510

Gnomad EAS exome AF: 0.00

Gnomad NFE exome AF: 0.0523

Gnomad OTH exome AF: 0.0486

GnomAD4 exome AF: 0.0509 AC: 133 AN: 2614 Hom.: 3 Cov.: 0 AF XY: 0.0498 AC XY: 67 AN XY: 1346

African (AFR) AF: 0.0811 AC: 6 AN: 74

American (AMR) AF: 0.125 AC: 1 AN: 8

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.0532 AC: 5 AN: 94

European-Finnish (FIN) AF: 0.0235 AC: 10 AN: 426

Middle Eastern (MID) AF: 0.0607 AC: 99 AN: 1632

European-Non Finnish (NFE) AF: 0.0385 AC: 7 AN: 182

Other (OTH) AF: 0.0258 AC: 5 AN: 194

GnomAD4 genome AF: 0.0431 AC: 6543 AN: 151844 Hom.: 155 Cov.: 32 AF XY: 0.0406 AC XY: 3016 AN XY: 74278

African (AFR) AF: 0.0467 AC: 1924 AN: 41226

American (AMR) AF: 0.0379 AC: 579 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.0586 AC: 203 AN: 3464

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.0172 AC: 83 AN: 4828

European-Finnish (FIN) AF: 0.0215 AC: 228 AN: 10596

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0481 AC: 3269 AN: 67970

Other (OTH) AF: 0.0375 AC: 79 AN: 2108

Alfa AF: 0.0340 Hom.: 42

Bravo AF: 0.0451

Asia WGS AF: 0.0150 AC: 53 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.2
DANN	Benign	0.76
PhyloP100		0.21

Splicing

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

Other links and lift over

dbSNP: rs11603185; hg19: chr11-81601884;