17-6655449-C-T

Variant names:

• chr17-6655449-C-T
• rs8078913
• ENST00000582609.1:n.61G>A

Variant summary

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

The ENST00000000000(MIR4520-1):​n.20G>A variant causes a splice region, non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 152,018 control chromosomes in the GnomAD database, including 22,589 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 0.54 (22543 hom., cov: 29)
  • Exomes 𝑓: 0.47 (46 hom.)
• Consequence: MIR4520-1 ENST00000000000 splice_region, non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.233
• Publications: 20 publications found

Genes affected

MIR4520-1 (HGNC:41775): (microRNA 4520-1) 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]

MIR4520-2 (HGNC:41839): (microRNA 4520-2) 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]

C17orf100 (HGNC:34494): (chromosome 17 open reading frame 100)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000582609.1. 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
	MIR4520-1	NR_039745.1		n.61G>A		non_coding_transcript_exon	Exon 1 of 1
	MIR4520-2	NR_039874.1		n.1C>T		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR4520-1	ENST00000582609.1	TSL:6	n.61G>A		non_coding_transcript_exon	Exon 1 of 1
	MIR4520-2	ENST00000636586.1	TSL:6	n.1C>T		non_coding_transcript_exon	Exon 1 of 1
	C17orf100	ENST00000634977.1	TSL:5	n.*324+2855C>T		intron	N/A	ENSP00000491769.1	A0A1W2PPW6

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82009 AN: 151540 Hom.: 22527 Cov.: 29

Gnomad AFR AF: 0.623

Gnomad AMI AF: 0.604

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.708

Gnomad SAS AF: 0.576

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.522

GnomAD2 exomes AF: 0.489 AC: 173 AN: 354 AF XY: 0.450

Gnomad AFR exome AF: 0.500

Gnomad FIN exome AF: 0.333

Gnomad NFE exome AF: 0.497

Gnomad OTH exome AF: 0.333

GnomAD4 exome AF: 0.475 AC: 171 AN: 360 Hom.: 46 Cov.: 0 AF XY: 0.481 AC XY: 76 AN XY: 158

African (AFR) AF: 0.625 AC: 5 AN: 8

American (AMR) AF: 0.750 AC: 6 AN: 8

Ashkenazi Jewish (ASJ) AF: 0.667 AC: 4 AN: 6

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.750 AC: 6 AN: 8

European-Finnish (FIN) AF: 0.500 AC: 2 AN: 4

Middle Eastern (MID) AF: 0.406 AC: 43 AN: 106

European-Non Finnish (NFE) AF: 0.495 AC: 90 AN: 182

Other (OTH) AF: 0.395 AC: 15 AN: 38

GnomAD4 genome AF: 0.541 AC: 82060 AN: 151658 Hom.: 22543 Cov.: 29 AF XY: 0.541 AC XY: 40081 AN XY: 74110

African (AFR) AF: 0.623 AC: 25737 AN: 41332

American (AMR) AF: 0.576 AC: 8789 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.440 AC: 1526 AN: 3470

East Asian (EAS) AF: 0.708 AC: 3614 AN: 5104

South Asian (SAS) AF: 0.575 AC: 2749 AN: 4784

European-Finnish (FIN) AF: 0.440 AC: 4634 AN: 10538

Middle Eastern (MID) AF: 0.541 AC: 158 AN: 292

European-Non Finnish (NFE) AF: 0.489 AC: 33195 AN: 67858

Other (OTH) AF: 0.526 AC: 1108 AN: 2108

Alfa AF: 0.354 Hom.: 895

Bravo AF: 0.556

Asia WGS AF: 0.647 AC: 2253 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	12
DANN	Benign	0.88
PhyloP100		0.23

Splicing

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

Other links and lift over

dbSNP: rs8078913; hg19: chr17-6558768; COSMIC: COSV104387558;