ENST00000710694.1:n.499+393A>G

Variant names:

• chr19-53748783-A-G
• rs4803178
• ENST00000710694.1:n.499+393A>G

Variant summary

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

The ENST00000710694.1(ENSG00000269842):​n.499+393A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0366 in 517,648 control chromosomes in the GnomAD database, including 435 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 0.034 (110 hom., cov: 32)
  • Exomes 𝑓: 0.037 (325 hom.)
• Consequence: ENSG00000269842 ENST00000710694.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347
• Publications: 2 publications found

Genes affected

ENSG00000269842 (HGNC:):

MIR521-1 (HGNC:32126): (microRNA 521-1) 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=-0.73).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0522 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000710694.1. 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
	MIR521-1	NR_030216.1		n.*61A>G		downstream_gene	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000269842	ENST00000710694.1		n.499+393A>G		intron	N/A
	ENSG00000269842	ENST00000710695.1		n.496+393A>G		intron	N/A
	ENSG00000269842	ENST00000710696.1		n.1357+393A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0344 AC: 5239 AN: 152124 Hom.: 110 Cov.: 32

Gnomad AFR AF: 0.0163

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0552

Gnomad ASJ AF: 0.0683

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0164

Gnomad FIN AF: 0.0321

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0432

Gnomad OTH AF: 0.0440

GnomAD4 exome AF: 0.0375 AC: 13687 AN: 365406 Hom.: 325 AF XY: 0.0360 AC XY: 7502 AN XY: 208434

African (AFR) AF: 0.0127 AC: 120 AN: 9432

American (AMR) AF: 0.0434 AC: 1367 AN: 31466

Ashkenazi Jewish (ASJ) AF: 0.0650 AC: 716 AN: 11016

East Asian (EAS) AF: 0.000154 AC: 2 AN: 13020

South Asian (SAS) AF: 0.0206 AC: 1312 AN: 63568

European-Finnish (FIN) AF: 0.0336 AC: 1076 AN: 32046

Middle Eastern (MID) AF: 0.0388 AC: 107 AN: 2756

European-Non Finnish (NFE) AF: 0.0448 AC: 8337 AN: 186194

Other (OTH) AF: 0.0409 AC: 650 AN: 15908

GnomAD4 genome AF: 0.0345 AC: 5247 AN: 152242 Hom.: 110 Cov.: 32 AF XY: 0.0334 AC XY: 2488 AN XY: 74416

African (AFR) AF: 0.0164 AC: 680 AN: 41580

American (AMR) AF: 0.0553 AC: 844 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0683 AC: 237 AN: 3470

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5170

South Asian (SAS) AF: 0.0168 AC: 81 AN: 4826

European-Finnish (FIN) AF: 0.0321 AC: 340 AN: 10596

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0432 AC: 2940 AN: 68012

Other (OTH) AF: 0.0435 AC: 92 AN: 2114

Alfa AF: 0.0389 Hom.: 118

Bravo AF: 0.0357

Asia WGS AF: 0.0120 AC: 41 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	2.1
DANN	Benign	0.44
PhyloP100		0.35

Splicing

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

Other links and lift over

dbSNP: rs4803178; hg19: chr19-54252037;