rs10865292

Variant names:

• chr2-55988917-G-A
• rs10865292
• ENST00000606639.1:n.82+36678G>A

Variant summary

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

The ENST00000606639.1(ENSG00000272180):​n.82+36678G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.91 in 481,352 control chromosomes in the GnomAD database, including 199,721 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 0.92 (64440 hom., cov: 32)
  • Exomes 𝑓: 0.91 (135281 hom.)
• Consequence: ENSG00000272180 ENST00000606639.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.205
• Publications: 7 publications found

Genes affected

ENSG00000272180 (HGNC:):

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

MIR216A (HGNC:31593): (microRNA 216a) 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000606639.1. 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
	MIR217HG	NR_126406.1		n.208+24692C>T		intron	N/A
	MIR216A	NR_029629.1		n.*33C>T		downstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000272180	ENST00000606639.1	TSL:1	n.82+36678G>A		intron	N/A
	MIR217HG	ENST00000446139.2	TSL:5	n.924+24692C>T		intron	N/A
	MIR217HG	ENST00000701602.1		n.407+4956C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.919 AC: 139890 AN: 152148 Hom.: 64384 Cov.: 32

Gnomad AFR AF: 0.957

Gnomad AMI AF: 0.927

Gnomad AMR AF: 0.908

Gnomad ASJ AF: 0.877

Gnomad EAS AF: 0.879

Gnomad SAS AF: 0.909

Gnomad FIN AF: 0.885

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.911

Gnomad OTH AF: 0.900

GnomAD2 exomes AF: 0.907 AC: 220509 AN: 243126 AF XY: 0.905

Gnomad AFR exome AF: 0.958

Gnomad AMR exome AF: 0.914

Gnomad ASJ exome AF: 0.881

Gnomad EAS exome AF: 0.872

Gnomad FIN exome AF: 0.879

Gnomad NFE exome AF: 0.911

Gnomad OTH exome AF: 0.909

GnomAD4 exome AF: 0.906 AC: 298269 AN: 329088 Hom.: 135281 Cov.: 0 AF XY: 0.905 AC XY: 166336 AN XY: 183700

African (AFR) AF: 0.955 AC: 9242 AN: 9680

American (AMR) AF: 0.913 AC: 31699 AN: 34716

Ashkenazi Jewish (ASJ) AF: 0.882 AC: 9438 AN: 10700

East Asian (EAS) AF: 0.869 AC: 10404 AN: 11970

South Asian (SAS) AF: 0.907 AC: 53381 AN: 58840

European-Finnish (FIN) AF: 0.879 AC: 26534 AN: 30170

Middle Eastern (MID) AF: 0.883 AC: 2339 AN: 2650

European-Non Finnish (NFE) AF: 0.912 AC: 142365 AN: 156150

Other (OTH) AF: 0.905 AC: 12867 AN: 14212

GnomAD4 genome AF: 0.919 AC: 140002 AN: 152264 Hom.: 64440 Cov.: 32 AF XY: 0.917 AC XY: 68232 AN XY: 74446

African (AFR) AF: 0.957 AC: 39761 AN: 41560

American (AMR) AF: 0.909 AC: 13900 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.877 AC: 3046 AN: 3472

East Asian (EAS) AF: 0.879 AC: 4548 AN: 5174

South Asian (SAS) AF: 0.909 AC: 4379 AN: 4818

European-Finnish (FIN) AF: 0.885 AC: 9382 AN: 10604

Middle Eastern (MID) AF: 0.867 AC: 255 AN: 294

European-Non Finnish (NFE) AF: 0.911 AC: 61993 AN: 68020

Other (OTH) AF: 0.896 AC: 1893 AN: 2112

Alfa AF: 0.914 Hom.: 87047

Bravo AF: 0.922

Asia WGS AF: 0.906 AC: 3150 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.71
DANN	Benign	0.65
PhyloP100		-0.20

Splicing

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

Other links and lift over

dbSNP: rs10865292; hg19: chr2-56216052;