rs2823897

Variant names:

• chr21-16590062-T-A
• rs2823897
• ENST00000659483.2:n.878T>A

Variant summary

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

The ENST00000659483.2(MIR99AHG):​n.878T>A 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 0.0421 in 152,286 control chromosomes in the GnomAD database, including 308 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 0.042 (308 hom., cov: 32)
• Consequence: MIR99AHG ENST00000659483.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.09

Genes affected

MIR99AHG (HGNC:1274): (mir-99a-let-7c cluster host gene)

MIR125B2 (HGNC:31507): (microRNA 125b-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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIR99AHG	NR_027790.3	n.580-4278T>A		intron_variant	Intron 6 of 7
MIR99AHG	NR_027791.3	n.498-16932T>A		intron_variant	Intron 5 of 5
MIR99AHG	NR_111004.2	n.564-16932T>A		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIR99AHG	ENST00000659483.2	n.878T>A		non_coding_transcript_exon_variant	Exon 2 of 2
MIR99AHG	ENST00000661403.1	n.1077T>A		non_coding_transcript_exon_variant	Exon 8 of 8
MIR99AHG	ENST00000663661.1	n.1643T>A		non_coding_transcript_exon_variant	Exon 9 of 9

Frequencies

GnomAD3 genomes AF: 0.0420 AC: 6397 AN: 152168 Hom.: 303 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0202

Gnomad ASJ AF: 0.0164

Gnomad EAS AF: 0.0148

Gnomad SAS AF: 0.0242

Gnomad FIN AF: 0.00264

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0131

Gnomad OTH AF: 0.0364

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0421 AC: 6417 AN: 152286 Hom.: 308 Cov.: 32 AF XY: 0.0411 AC XY: 3060 AN XY: 74470

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.0202

Gnomad4 ASJ AF: 0.0164

Gnomad4 EAS AF: 0.0148

Gnomad4 SAS AF: 0.0240

Gnomad4 FIN AF: 0.00264

Gnomad4 NFE AF: 0.0131

Gnomad4 OTH AF: 0.0360

Alfa AF: 0.0287 Hom.: 19

Bravo AF: 0.0469

Asia WGS AF: 0.0370 AC: 129 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	16
DANN	Benign	0.67

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2823897; hg19: chr21-17962382;