Genetic Variant ENST00000710694.1:n.499+393A>G (chr19-53748783-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.347

Variant links:

Genes affected

ENSG00000269842 (HGNC:):

ENSG00000269842 links:

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]

MIR521-1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
LOC124904765	XR_007067333.1 link	n.847+393A>G	intron_variant	Intron 4 of 4
LOC124904765	XR_007067334.1 link	n.939+393A>G	intron_variant	Intron 5 of 5
MIR521-1	NR_030216.1 link	n.*61A>G	downstream_gene_variant
MIR521-1	unassigned_transcript_3383	n.*73A>G	downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank
ENSG00000269842	ENST00000710694.1 link	n.499+393A>G	intron_variant	Intron 3 of 4
ENSG00000269842	ENST00000710695.1 link	n.496+393A>G	intron_variant	Intron 3 of 3
ENSG00000269842	ENST00000710696.1 link	n.1357+393A>G	intron_variant	Intron 10 of 11

Frequencies

GnomAD3 genomes

AF:

0.0344

AC:

5239

AN:

152124

Hom.:

110

Cov.:

show subpopulations

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

show subpopulations

Gnomad4 AFR exome

AF:

0.0127

Gnomad4 AMR exome

AF:

0.0434

Gnomad4 ASJ exome

AF:

0.0650

Gnomad4 EAS exome

AF:

0.000154

Gnomad4 SAS exome

AF:

0.0206

Gnomad4 FIN exome

AF:

0.0336

Gnomad4 NFE exome

AF:

0.0448

Gnomad4 OTH exome

AF:

0.0409

GnomAD4 genome

AF:

0.0345

AC:

5247

AN:

152242

Hom.:

110

Cov.:

AF XY:

0.0334

AC XY:

2488

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.0164

Gnomad4 AMR

AF:

0.0553

Gnomad4 ASJ

AF:

0.0683

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.0168

Gnomad4 FIN

AF:

0.0321

Gnomad4 NFE

AF:

0.0432

Gnomad4 OTH

AF:

0.0435

Alfa

AF:

0.0383

Hom.:

Bravo

AF:

0.0357

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

2.1

DANN

Benign

0.44

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over