19-53788578-C-T

Variant names:

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

Variant summary

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

The ENST00000597420.2(ENSG00000269564):​n.90-19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 459,238 control chromosomes in the GnomAD database, including 5,998 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 0.15 (1849 hom., cov: 32)
  • Exomes 𝑓: 0.16 (4149 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.185 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.-127C>T		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000269564	ENST00000597420.2	TSL:6	n.90-19C>T		intron	N/A
	MIR373	ENST00000362273.1	TSL:6	n.-127C>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23088 AN: 151486 Hom.: 1851 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.0794

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.132

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.128

GnomAD4 exome AF: 0.158 AC: 48674 AN: 307666 Hom.: 4149 AF XY: 0.162 AC XY: 28238 AN XY: 174536

African (AFR) AF: 0.159 AC: 1303 AN: 8188

American (AMR) AF: 0.146 AC: 3769 AN: 25790

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 1221 AN: 10296

East Asian (EAS) AF: 0.0676 AC: 611 AN: 9034

South Asian (SAS) AF: 0.205 AC: 12019 AN: 58638

European-Finnish (FIN) AF: 0.177 AC: 4098 AN: 23180

Middle Eastern (MID) AF: 0.113 AC: 291 AN: 2566

European-Non Finnish (NFE) AF: 0.150 AC: 23359 AN: 156002

Other (OTH) AF: 0.143 AC: 2003 AN: 13972

GnomAD4 genome AF: 0.152 AC: 23095 AN: 151572 Hom.: 1849 Cov.: 32 AF XY: 0.154 AC XY: 11423 AN XY: 74006

African (AFR) AF: 0.158 AC: 6528 AN: 41318

American (AMR) AF: 0.142 AC: 2163 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 422 AN: 3464

East Asian (EAS) AF: 0.0791 AC: 407 AN: 5146

South Asian (SAS) AF: 0.195 AC: 938 AN: 4798

European-Finnish (FIN) AF: 0.190 AC: 1973 AN: 10388

Middle Eastern (MID) AF: 0.126 AC: 36 AN: 286

European-Non Finnish (NFE) AF: 0.150 AC: 10186 AN: 67926

Other (OTH) AF: 0.126 AC: 265 AN: 2100

Alfa AF: 0.142 Hom.: 2825

Bravo AF: 0.146

Asia WGS AF: 0.156 AC: 540 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.0
DANN	Benign	0.32
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; COSMIC: COSV107454421;