chr19-53697365-G-A

Variant names:

• chr19-53697365-G-A
• rs1989486
• ENST00000710708.1:n.462+6959G>A

Variant summary

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

The ENST00000710708.1(ENSG00000269842):​n.462+6959G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 151,960 control chromosomes in the GnomAD database, including 25,308 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 0.55 (25308 hom., cov: 32)
• Consequence: ENSG00000269842 ENST00000710708.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• Publications: 4 publications found

Genes affected

ENSG00000269842 (HGNC:):

MIR525 (HGNC:32102): (microRNA 525) 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.788 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIR525	NR_030192.1	n.-168G>A		upstream_gene_variant
MIR525	unassigned_transcript_3339	n.-182G>A		upstream_gene_variant
MIR525	unassigned_transcript_3340	n.-219G>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000269842	ENST00000710708.1	n.462+6959G>A		intron_variant	Intron 3 of 9
ENSG00000269842	ENST00000728578.1	n.473-121G>A		intron_variant	Intron 3 of 3
MIR525	ENST00000384978.1	n.-168G>A		upstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.554 AC: 84090 AN: 151842 Hom.: 25261 Cov.: 32

Gnomad AFR AF: 0.795

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.650

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.518

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

GnomAD4 genome AF: 0.554 AC: 84204 AN: 151960 Hom.: 25308 Cov.: 32 AF XY: 0.554 AC XY: 41135 AN XY: 74268

African (AFR) AF: 0.795 AC: 32951 AN: 41450

American (AMR) AF: 0.470 AC: 7169 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 1473 AN: 3470

East Asian (EAS) AF: 0.651 AC: 3357 AN: 5158

South Asian (SAS) AF: 0.618 AC: 2970 AN: 4806

European-Finnish (FIN) AF: 0.424 AC: 4476 AN: 10558

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.445 AC: 30223 AN: 67938

Other (OTH) AF: 0.519 AC: 1094 AN: 2108

Alfa AF: 0.510 Hom.: 2612

Bravo AF: 0.567

Asia WGS AF: 0.655 AC: 2277 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	0.93
DANN	Benign	0.63
PhyloP100		-1.0

Splicing

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

Other links and lift over

dbSNP: rs1989486; hg19: chr19-54200619;