chr19-53688489-A-G

Variant names:

• chr19-53688489-A-G
• rs57111412
• ENST00000408494.1:n.9A>G

Variant summary

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

The ENST00000408494.1(MIR1283-1):​n.9A>G 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 0.149 in 530,934 control chromosomes in the GnomAD database, including 9,479 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 0.19 (4632 hom., cov: 32)
  • Exomes 𝑓: 0.13 (4847 hom.)
• Consequence: MIR1283-1 ENST00000408494.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.529
• Publications: 13 publications found

Genes affected

MIR1283-1 (HGNC:35255): (microRNA 1283-1) 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]

ENSG00000269842 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIR1283-1	NR_031573.1	n.9A>G		non_coding_transcript_exon_variant	Exon 1 of 1
LOC107985342	XR_007067332.1	n.356-5540A>G		intron_variant	Intron 2 of 2
MIR1283-1	unassigned_transcript_3332	n.-5A>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIR1283-1	ENST00000408494.1	n.9A>G		non_coding_transcript_exon_variant	Exon 1 of 1	6
ENSG00000269842	ENST00000710736.1	n.640A>G		non_coding_transcript_exon_variant	Exon 2 of 2
ENSG00000269842	ENST00000710708.1	n.349-1804A>G		intron_variant	Intron 2 of 9

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29528 AN: 152006 Hom.: 4623 Cov.: 32

Gnomad AFR AF: 0.425

Gnomad AMI AF: 0.0672

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.0950

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0736

Gnomad OTH AF: 0.182

GnomAD2 exomes AF: 0.149 AC: 36763 AN: 247208 AF XY: 0.146

Gnomad AFR exome AF: 0.430

Gnomad AMR exome AF: 0.159

Gnomad ASJ exome AF: 0.107

Gnomad EAS exome AF: 0.285

Gnomad FIN exome AF: 0.0967

Gnomad NFE exome AF: 0.0737

Gnomad OTH exome AF: 0.116

GnomAD4 exome AF: 0.131 AC: 49657 AN: 378810 Hom.: 4847 Cov.: 0 AF XY: 0.136 AC XY: 29459 AN XY: 215952

African (AFR) AF: 0.421 AC: 4276 AN: 10148

American (AMR) AF: 0.160 AC: 5571 AN: 34886

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 1218 AN: 11682

East Asian (EAS) AF: 0.270 AC: 3551 AN: 13142

South Asian (SAS) AF: 0.235 AC: 15468 AN: 65816

European-Finnish (FIN) AF: 0.0978 AC: 3159 AN: 32290

Middle Eastern (MID) AF: 0.140 AC: 399 AN: 2844

European-Non Finnish (NFE) AF: 0.0729 AC: 13945 AN: 191408

Other (OTH) AF: 0.125 AC: 2070 AN: 16594

GnomAD4 genome AF: 0.194 AC: 29586 AN: 152124 Hom.: 4632 Cov.: 32 AF XY: 0.196 AC XY: 14570 AN XY: 74382

African (AFR) AF: 0.425 AC: 17601 AN: 41462

American (AMR) AF: 0.160 AC: 2449 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 399 AN: 3472

East Asian (EAS) AF: 0.273 AC: 1411 AN: 5162

South Asian (SAS) AF: 0.256 AC: 1236 AN: 4830

European-Finnish (FIN) AF: 0.0950 AC: 1008 AN: 10608

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0736 AC: 5003 AN: 67990

Other (OTH) AF: 0.185 AC: 391 AN: 2112

Alfa AF: 0.124 Hom.: 985

Bravo AF: 0.207

Asia WGS AF: 0.282 AC: 980 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.4
DANN	Benign	0.33
PhyloP100		-0.53

Splicing

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

Other links and lift over

dbSNP: rs57111412; hg19: chr19-54191743; COSMIC: COSV66023764;