19-53719910-C-T

Variant names:

• chr19-53719910-C-T
• rs2217653
• ENST00000710708.1:n.585+6809C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000710708.1(ENSG00000269842):​n.585+6809C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.778 in 152,192 control chromosomes in the GnomAD database, including 46,858 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 0.78 (46858 hom., cov: 33)
• Consequence: ENSG00000269842 ENST00000710708.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.653

Genes affected

ENSG00000269842 (HGNC:):

MIR520D (HGNC:32114): (microRNA 520d) 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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.916 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIR520D	NR_030204.1	n.-186C>T		upstream_gene_variant
MIR520D	unassigned_transcript_3361	n.-201C>T		upstream_gene_variant
MIR520D	unassigned_transcript_3362	n.-239C>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000269842	ENST00000710708.1	n.585+6809C>T		intron_variant	Intron 4 of 9
MIR520D	ENST00000385002.1	n.-186C>T		upstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.778 AC: 118356 AN: 152074 Hom.: 46812 Cov.: 33

Gnomad AFR AF: 0.924

Gnomad AMI AF: 0.766

Gnomad AMR AF: 0.663

Gnomad ASJ AF: 0.797

Gnomad EAS AF: 0.792

Gnomad SAS AF: 0.680

Gnomad FIN AF: 0.711

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.732

Gnomad OTH AF: 0.763

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.778 AC: 118460 AN: 152192 Hom.: 46858 Cov.: 33 AF XY: 0.772 AC XY: 57430 AN XY: 74394

Gnomad4 AFR AF: 0.924

Gnomad4 AMR AF: 0.663

Gnomad4 ASJ AF: 0.797

Gnomad4 EAS AF: 0.792

Gnomad4 SAS AF: 0.680

Gnomad4 FIN AF: 0.711

Gnomad4 NFE AF: 0.732

Gnomad4 OTH AF: 0.764

Alfa AF: 0.767 Hom.: 5639

Bravo AF: 0.785

Asia WGS AF: 0.777 AC: 2703 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.4
DANN	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2217653; hg19: chr19-54223164; COSMIC: COSV66008938;