17-62944250-A-G

Variant names:

• chr17-62944250-A-G
• rs17759989
• ENST00000384821.1:n.36A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000384821.1(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 ENST00000384821.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.464
• Publications: 12 publications found

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]

ENSG00000283538 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 78 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000384821.1. 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
	MIR633	NR_030363.1		n.36A>G		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR633	ENST00000384821.1	TSL:6	n.36A>G		non_coding_transcript_exon	Exon 1 of 1
	ENSG00000283538	ENST00000636248.2	TSL:5	n.51-7385T>C		intron	N/A
	ENSG00000283538	ENST00000650312.1		n.128-7385T>C		intron	N/A

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

GnomAD2 exomes AF: 0.0258 AC: 6348 AN: 245632 AF XY: 0.0268

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 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

African (AFR) AF: 0.0333 AC: 347 AN: 10414

American (AMR) AF: 0.0110 AC: 395 AN: 36006

Ashkenazi Jewish (ASJ) AF: 0.0109 AC: 127 AN: 11688

East Asian (EAS) AF: 0.00502 AC: 66 AN: 13156

South Asian (SAS) AF: 0.0371 AC: 2463 AN: 66302

European-Finnish (FIN) AF: 0.0351 AC: 1128 AN: 32174

Middle Eastern (MID) AF: 0.0570 AC: 162 AN: 2842

European-Non Finnish (NFE) AF: 0.0293 AC: 5616 AN: 191572

Other (OTH) AF: 0.0317 AC: 529 AN: 16680

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

African (AFR) AF: 0.0313 AC: 1302 AN: 41556

American (AMR) AF: 0.0195 AC: 298 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00864 AC: 30 AN: 3472

East Asian (EAS) AF: 0.00559 AC: 29 AN: 5190

South Asian (SAS) AF: 0.0367 AC: 177 AN: 4824

European-Finnish (FIN) AF: 0.0382 AC: 405 AN: 10608

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0278 AC: 1892 AN: 68026

Other (OTH) AF: 0.0275 AC: 58 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.0
DANN	Benign	0.32
PhyloP100		0.46

Splicing

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

Other links and lift over

dbSNP: rs17759989; hg19: chr17-61021611;