17-6655449-C-T

Variant names:

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

Variant summary

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

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 splice_region, non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.233

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIR4520-1	NR_039745.1	n.61G>A		non_coding_transcript_exon_variant	Exon 1 of 1
MIR4520-2	NR_039874.1	n.1C>T		non_coding_transcript_exon_variant	Exon 1 of 1
MIR4520-1	unassigned_transcript_2929	n.20G>A		splice_region_variant, non_coding_transcript_exon_variant	Exon 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIR4520-1	ENST00000582609.1	n.61G>A		non_coding_transcript_exon_variant	Exon 1 of 1	6
MIR4520-2	ENST00000636586.1	n.1C>T		non_coding_transcript_exon_variant	Exon 1 of 1	6
C17orf100	ENST00000634977.1	n.*324+2855C>T		intron_variant	Intron 1 of 1	5		ENSP00000491769.1
C17orf100	ENST00000635042.1	n.*324+2855C>T		intron_variant	Intron 1 of 1	5		ENSP00000491523.1

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

GnomAD3 exomes AF: 0.489 AC: 173 AN: 354 Hom.: 39 AF XY: 0.450 AC XY: 91 AN XY: 202

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

Gnomad4 AFR exome AF: 0.625

Gnomad4 AMR exome AF: 0.750

Gnomad4 ASJ exome AF: 0.667

Gnomad4 SAS exome AF: 0.750

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.495

Gnomad4 OTH exome AF: 0.395

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

Gnomad4 AFR AF: 0.623

Gnomad4 AMR AF: 0.576

Gnomad4 ASJ AF: 0.440

Gnomad4 EAS AF: 0.708

Gnomad4 SAS AF: 0.575

Gnomad4 FIN AF: 0.440

Gnomad4 NFE AF: 0.489

Gnomad4 OTH AF: 0.526

Alfa AF: 0.334 Hom.: 759

Bravo AF: 0.556

Asia WGS AF: 0.647 AC: 2253 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

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