rs41291173

chr2-55983005-G-Achr2-55983005-G-C

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4 BS1 BS2

The NR_029630.1(MIR217):n.72C>T variant causes a non coding transcript exon change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0141 in 532,846 control chromosomes in the GnomAD database, including 86 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 0.014 (25 hom., cov: 32)
  • Exomes 𝑓: 0.014 (61 hom.)
• Consequence: MIR217 NR_029630.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.46

Genes affected

MIR217 (HGNC:31594): (microRNA 217) 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]

MIR217HG (HGNC:50537): (MIR217 host gene)

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.18).
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0141 (2152/152268) while in subpopulation AMR AF= 0.0275 (421/15310). AF 95% confidence interval is 0.0253. There are 25 homozygotes in gnomad4. There are 985 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 25 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MIR217	NR_029630.1	n.72C>T		non_coding_transcript_exon_variant	1/1
MIR217HG	NR_126406.1	n.209-19123C>T		intron_variant, non_coding_transcript_variant
LOC105374690	XR_940109.3	n.587+30766G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIR217	ENST00000384817.3	n.72C>T		non_coding_transcript_exon_variant	1/1
MIR217HG	ENST00000446139.1	n.209-19123C>T		intron_variant, non_coding_transcript_variant		5
	ENST00000606639.1	n.82+30766G>A		intron_variant, non_coding_transcript_variant		1
MIR217HG	ENST00000701602.1	n.407+10868C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0142 AC: 2153 AN: 152150 Hom.: 25 Cov.: 32

Gnomad AFR AF: 0.00500

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0275

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.00679

Gnomad MID AF: 0.0223

Gnomad NFE AF: 0.0201

Gnomad OTH AF: 0.0230

GnomAD3 exomes AF: 0.0135 AC: 3356 AN: 247852 Hom.: 42 AF XY: 0.0135 AC XY: 1812 AN XY: 134158

Gnomad AFR exome AF: 0.00420

Gnomad AMR exome AF: 0.0162

Gnomad ASJ exome AF: 0.00511

Gnomad EAS exome AF: 0.000110

Gnomad SAS exome AF: 0.00411

Gnomad FIN exome AF: 0.00947

Gnomad NFE exome AF: 0.0202

Gnomad OTH exome AF: 0.0156

GnomAD4 exome AF: 0.0140 AC: 5338 AN: 380578 Hom.: 61 Cov.: 0 AF XY: 0.0133 AC XY: 2888 AN XY: 216602

Gnomad4 AFR exome AF: 0.00392

Gnomad4 AMR exome AF: 0.0161

Gnomad4 ASJ exome AF: 0.00496

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00420

Gnomad4 FIN exome AF: 0.0101

Gnomad4 NFE exome AF: 0.0198

Gnomad4 OTH exome AF: 0.0140

GnomAD4 genome AF: 0.0141 AC: 2152 AN: 152268 Hom.: 25 Cov.: 32 AF XY: 0.0132 AC XY: 985 AN XY: 74458

Gnomad4 AFR AF: 0.00498

Gnomad4 AMR AF: 0.0275

Gnomad4 ASJ AF: 0.00490

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00291

Gnomad4 FIN AF: 0.00679

Gnomad4 NFE AF: 0.0201

Gnomad4 OTH AF: 0.0227

Alfa AF: 0.0137 Hom.: 4

Bravo AF: 0.0146

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.18
Cadd	Benign	19
Dann	Benign	0.87

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs41291173; hg19: chr2-56210140;