rs12983273

Variant names:

• chr19-53788578-C-A
• rs12983273
• ENST00000597420.2:n.90-19C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-53788578-C-A
• chr19-53788578-C-G
• chr19-53788578-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000597420.2(ENSG00000269564):​n.90-19C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000065 in 307,854 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000065 (0 hom.)
• Consequence: ENSG00000269564 ENST00000597420.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305
• Publications: 23 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIR373	NR_029866.1	n.-127C>A		upstream_gene_variant
MIR373	unassigned_transcript_3402	n.-132C>A		upstream_gene_variant
MIR373	unassigned_transcript_3403	n.-170C>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000269564	ENST00000597420.2	n.90-19C>A		intron_variant	Intron 1 of 1	6
MIR373	ENST00000362273.1	n.-127C>A		upstream_gene_variant		6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000650 AC: 2 AN: 307854 Hom.: 0 AF XY: 0.00000573 AC XY: 1 AN XY: 174652

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 8194

American (AMR) AF: 0.00 AC: 0 AN: 25818

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10304

East Asian (EAS) AF: 0.00 AC: 0 AN: 9034

South Asian (SAS) AF: 0.0000170 AC: 1 AN: 58672

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23208

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2572

European-Non Finnish (NFE) AF: 0.00000641 AC: 1 AN: 156066

Other (OTH) AF: 0.00 AC: 0 AN: 13986

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00666416), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 2825

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.41
PhyloP100		0.30

Splicing

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

Other links and lift over

dbSNP: rs12983273; hg19: chr19-54291832;