19-53788035-C-T

Variant names:

• chr19-53788035-C-T
• rs28461391
• ENST00000595160.2:n.178G>A

Variant summary

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

The ENST00000595160.2(ENSG00000269877):​n.178G>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 0.116 in 389,630 control chromosomes in the GnomAD database, including 2,979 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 0.13 (1520 hom., cov: 31)
  • Exomes 𝑓: 0.11 (1459 hom.)
• Consequence: ENSG00000269877 ENST00000595160.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.271
• Publications: 8 publications found

Genes affected

ENSG00000269877 (HGNC:):

MIR372 (HGNC:31786): (microRNA 372) 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000595160.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR372	NR_029865.1		n.*79C>T		downstream_gene	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000269877	ENST00000595160.2	TSL:3	n.178G>A		non_coding_transcript_exon	Exon 1 of 2
	ENSG00000269564	ENST00000597420.2	TSL:6	n.90-562C>T		intron	N/A
	ENSG00000269877	ENST00000775521.1		n.73+94G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20260 AN: 151820 Hom.: 1512 Cov.: 31

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.0747

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.0972

Gnomad FIN AF: 0.0796

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.136

GnomAD4 exome AF: 0.105 AC: 24998 AN: 237692 Hom.: 1459 Cov.: 0 AF XY: 0.103 AC XY: 13476 AN XY: 130698

African (AFR) AF: 0.187 AC: 1243 AN: 6662

American (AMR) AF: 0.110 AC: 2052 AN: 18718

Ashkenazi Jewish (ASJ) AF: 0.0814 AC: 544 AN: 6682

East Asian (EAS) AF: 0.134 AC: 1230 AN: 9212

South Asian (SAS) AF: 0.0891 AC: 4160 AN: 46696

European-Finnish (FIN) AF: 0.0797 AC: 1852 AN: 23248

Middle Eastern (MID) AF: 0.0649 AC: 127 AN: 1958

European-Non Finnish (NFE) AF: 0.111 AC: 12711 AN: 114188

Other (OTH) AF: 0.104 AC: 1079 AN: 10328

GnomAD4 genome AF: 0.134 AC: 20294 AN: 151938 Hom.: 1520 Cov.: 31 AF XY: 0.131 AC XY: 9710 AN XY: 74274

African (AFR) AF: 0.193 AC: 8007 AN: 41434

American (AMR) AF: 0.132 AC: 2010 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.0747 AC: 259 AN: 3466

East Asian (EAS) AF: 0.119 AC: 612 AN: 5124

South Asian (SAS) AF: 0.0969 AC: 467 AN: 4820

European-Finnish (FIN) AF: 0.0796 AC: 842 AN: 10584

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7657 AN: 68000

Other (OTH) AF: 0.143 AC: 302 AN: 2108

Alfa AF: 0.122 Hom.: 1881

Bravo AF: 0.141

Asia WGS AF: 0.152 AC: 528 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.6
DANN	Benign	0.86
PhyloP100		-0.27

Splicing

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

Other links and lift over

dbSNP: rs28461391; hg19: chr19-54291289;