19-53731099-A-G

Variant names:

• chr19-53731099-A-G
• rs4470257
• ENST00000710708.1:n.586-15104A>G

Variant summary

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

The ENST00000710708.1(ENSG00000269842):​n.586-15104A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 522,218 control chromosomes in the GnomAD database, including 5,896 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 0.16 (2454 hom., cov: 31)
  • Exomes 𝑓: 0.13 (3442 hom.)
• Consequence: ENSG00000269842 ENST00000710708.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59
• Publications: 8 publications found

Genes affected

ENSG00000269842 (HGNC:):

MIR518A1 (HGNC:32120): (microRNA 518a-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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIR518A1	NR_030210.1	n.*9A>G		downstream_gene_variant
MIR518A1	unassigned_transcript_3372	n.*61A>G		downstream_gene_variant
MIR518A1	unassigned_transcript_3373	n.*22A>G		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000269842	ENST00000710708.1	n.586-15104A>G		intron_variant	Intron 4 of 9
MIR518A1	ENST00000385068.1	n.*9A>G		downstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24641 AN: 151782 Hom.: 2444 Cov.: 31

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.108

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.0744

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.134

GnomAD2 exomes AF: 0.134 AC: 32882 AN: 244966 AF XY: 0.131

Gnomad AFR exome AF: 0.280

Gnomad AMR exome AF: 0.134

Gnomad ASJ exome AF: 0.0719

Gnomad EAS exome AF: 0.139

Gnomad FIN exome AF: 0.197

Gnomad NFE exome AF: 0.107

Gnomad OTH exome AF: 0.120

GnomAD4 exome AF: 0.128 AC: 47526 AN: 370318 Hom.: 3442 Cov.: 0 AF XY: 0.127 AC XY: 26607 AN XY: 209958

African (AFR) AF: 0.285 AC: 2832 AN: 9938

American (AMR) AF: 0.134 AC: 4591 AN: 34276

Ashkenazi Jewish (ASJ) AF: 0.0703 AC: 812 AN: 11556

East Asian (EAS) AF: 0.133 AC: 1712 AN: 12848

South Asian (SAS) AF: 0.132 AC: 8561 AN: 64680

European-Finnish (FIN) AF: 0.193 AC: 6228 AN: 32230

Middle Eastern (MID) AF: 0.114 AC: 319 AN: 2806

European-Non Finnish (NFE) AF: 0.111 AC: 20549 AN: 185782

Other (OTH) AF: 0.119 AC: 1922 AN: 16202

GnomAD4 genome AF: 0.162 AC: 24675 AN: 151900 Hom.: 2454 Cov.: 31 AF XY: 0.165 AC XY: 12277 AN XY: 74264

African (AFR) AF: 0.276 AC: 11417 AN: 41416

American (AMR) AF: 0.117 AC: 1785 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0744 AC: 258 AN: 3468

East Asian (EAS) AF: 0.135 AC: 692 AN: 5126

South Asian (SAS) AF: 0.127 AC: 613 AN: 4808

European-Finnish (FIN) AF: 0.193 AC: 2039 AN: 10548

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.110 AC: 7449 AN: 67962

Other (OTH) AF: 0.135 AC: 283 AN: 2104

Alfa AF: 0.136 Hom.: 1153

Bravo AF: 0.161

Asia WGS AF: 0.140 AC: 486 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	0.48
DANN	Benign	0.12
PhyloP100		-1.6
Mutation Taster		=99/1	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs4470257; hg19: chr19-54234353; COSMIC: COSV66067106;