rs17759989

chr17-62944250-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NR_030363.1(MIR633):n.36A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0283 in 533,120 control chromosomes in the GnomAD database, including 303 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 0.028 (78 hom., cov: 32)
  • Exomes 𝑓: 0.028 (225 hom.)
• Consequence: MIR633 NR_030363.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.464

Genes affected

MIR633 (HGNC:32889): (microRNA 633) 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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0278 (4232/152286) while in subpopulation SAS AF= 0.0367 (177/4824). AF 95% confidence interval is 0.0323. There are 78 homozygotes in gnomad4. There are 2069 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 77 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MIR633	NR_030363.1	n.36A>G		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIR633	ENST00000384821.1	n.36A>G		non_coding_transcript_exon_variant	1/1
	ENST00000636248.2	n.51-7385T>C		intron_variant, non_coding_transcript_variant		5
	ENST00000650312.1	n.128-7385T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0277 AC: 4221 AN: 152168 Hom.: 77 Cov.: 32

Gnomad AFR AF: 0.0313

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0195

Gnomad ASJ AF: 0.00864

Gnomad EAS AF: 0.00557

Gnomad SAS AF: 0.0360

Gnomad FIN AF: 0.0382

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0278

Gnomad OTH AF: 0.0263

GnomAD3 exomes AF: 0.0258 AC: 6348 AN: 245632 Hom.: 106 AF XY: 0.0268 AC XY: 3565 AN XY: 133182

Gnomad AFR exome AF: 0.0325

Gnomad AMR exome AF: 0.0113

Gnomad ASJ exome AF: 0.0103

Gnomad EAS exome AF: 0.00618

Gnomad SAS exome AF: 0.0365

Gnomad FIN exome AF: 0.0357

Gnomad NFE exome AF: 0.0290

Gnomad OTH exome AF: 0.0296

GnomAD4 exome AF: 0.0284 AC: 10833 AN: 380834 Hom.: 225 Cov.: 0 AF XY: 0.0297 AC XY: 6437 AN XY: 216822

Gnomad4 AFR exome AF: 0.0333

Gnomad4 AMR exome AF: 0.0110

Gnomad4 ASJ exome AF: 0.0109

Gnomad4 EAS exome AF: 0.00502

Gnomad4 SAS exome AF: 0.0371

Gnomad4 FIN exome AF: 0.0351

Gnomad4 NFE exome AF: 0.0293

Gnomad4 OTH exome AF: 0.0317

GnomAD4 genome AF: 0.0278 AC: 4232 AN: 152286 Hom.: 78 Cov.: 32 AF XY: 0.0278 AC XY: 2069 AN XY: 74458

Gnomad4 AFR AF: 0.0313

Gnomad4 AMR AF: 0.0195

Gnomad4 ASJ AF: 0.00864

Gnomad4 EAS AF: 0.00559

Gnomad4 SAS AF: 0.0367

Gnomad4 FIN AF: 0.0382

Gnomad4 NFE AF: 0.0278

Gnomad4 OTH AF: 0.0275

Alfa AF: 0.0279 Hom.: 31

Bravo AF: 0.0260

Asia WGS AF: 0.0340 AC: 119 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	3.0
Dann	Benign	0.32

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17759989; hg19: chr17-61021611;