rs10425222

Variant names:

• chr19-53788945-C-A
• rs10425222
• ENST00000597420.2:n.438C>A

Variant summary

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

The ENST00000597420.2(ENSG00000269564):​n.438C>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 0.0687 in 299,482 control chromosomes in the GnomAD database, including 1,281 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 0.083 (847 hom., cov: 32)
  • Exomes 𝑓: 0.054 (434 hom.)
• Consequence: ENSG00000269564 ENST00000597420.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.694
• Publications: 11 publications found

Genes affected

ENSG00000269564 (HGNC:):

MIR373 (HGNC:31787): (microRNA 373) 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000597420.2. 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
	MIR373	NR_029866.1		n.*172C>A		downstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000269564	ENST00000597420.2	TSL:6	n.438C>A		non_coding_transcript_exon	Exon 2 of 2
	MIR373	ENST00000362273.1	TSL:6	n.*172C>A		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.0828 AC: 12567 AN: 151802 Hom.: 847 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.0648

Gnomad AMR AF: 0.0618

Gnomad ASJ AF: 0.0164

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.0174

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0342

Gnomad OTH AF: 0.0772

GnomAD4 exome AF: 0.0541 AC: 7989 AN: 147562 Hom.: 434 Cov.: 0 AF XY: 0.0608 AC XY: 4969 AN XY: 81704

African (AFR) AF: 0.179 AC: 419 AN: 2344

American (AMR) AF: 0.0434 AC: 242 AN: 5576

Ashkenazi Jewish (ASJ) AF: 0.0217 AC: 65 AN: 3000

East Asian (EAS) AF: 0.101 AC: 362 AN: 3602

South Asian (SAS) AF: 0.111 AC: 3602 AN: 32488

European-Finnish (FIN) AF: 0.0147 AC: 170 AN: 11590

Middle Eastern (MID) AF: 0.0551 AC: 26 AN: 472

European-Non Finnish (NFE) AF: 0.0339 AC: 2770 AN: 81762

Other (OTH) AF: 0.0495 AC: 333 AN: 6728

GnomAD4 genome AF: 0.0828 AC: 12576 AN: 151920 Hom.: 847 Cov.: 32 AF XY: 0.0822 AC XY: 6102 AN XY: 74268

African (AFR) AF: 0.184 AC: 7607 AN: 41418

American (AMR) AF: 0.0616 AC: 938 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.0164 AC: 57 AN: 3466

East Asian (EAS) AF: 0.121 AC: 623 AN: 5160

South Asian (SAS) AF: 0.126 AC: 602 AN: 4790

European-Finnish (FIN) AF: 0.0174 AC: 184 AN: 10586

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0342 AC: 2326 AN: 67962

Other (OTH) AF: 0.0797 AC: 168 AN: 2108

Alfa AF: 0.0496 Hom.: 67

Bravo AF: 0.0897

Asia WGS AF: 0.186 AC: 648 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.77
DANN	Benign	0.32
PhyloP100		-0.69

Splicing

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

Other links and lift over

dbSNP: rs10425222; hg19: chr19-54292199;