chr2-113583051-C-A

Variant names:

• chr2-113583051-C-A
• rs7589328
• ENST00000408128.1:n.46G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000408128.1(MIR1302-3):​n.46G>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. 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 0.000041 (0 hom., cov: 70)
  • Exomes 𝑓: 0.000018 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MIR1302-3 ENST00000408128.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.936
• Publications: 7 publications found

Genes affected

MIR1302-3 (HGNC:35295): (microRNA 1302-3) 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]

ENSG00000287165 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIR1302-3	NR_031632.1	n.46G>T		non_coding_transcript_exon_variant	Exon 1 of 1
LOC124907875	XR_007087203.1	n.996G>T		non_coding_transcript_exon_variant	Exon 1 of 2
LOC124907875	XR_007087204.1	n.980G>T		non_coding_transcript_exon_variant	Exon 1 of 3
MIR1302-3	unassigned_transcript_479	n.-27G>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIR1302-3	ENST00000408128.1	n.46G>T		non_coding_transcript_exon_variant	Exon 1 of 1	6
ENSG00000287165	ENST00000666960.2	n.995G>T		non_coding_transcript_exon_variant	Exon 1 of 2
ENSG00000291134	ENST00000801450.1	n.421-5499C>A		intron_variant	Intron 4 of 12

Frequencies

GnomAD3 genomes AF: 0.0000405 AC: 6 AN: 148030 Hom.: 0 Cov.: 70

Gnomad AFR AF: 0.0000247

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000199

Gnomad SAS AF: 0.000216

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000453

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000124 AC: 2 AN: 160910 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000262

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000180 AC: 6 AN: 333742 Hom.: 0 Cov.: 0 AF XY: 0.0000158 AC XY: 3 AN XY: 190018

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 9090

American (AMR) AF: 0.000101 AC: 3 AN: 29632

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10272

East Asian (EAS) AF: 0.00 AC: 0 AN: 11456

South Asian (SAS) AF: 0.0000331 AC: 2 AN: 60412

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27498

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1092

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 169698

Other (OTH) AF: 0.0000685 AC: 1 AN: 14592

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000405 AC: 6 AN: 148142 Hom.: 0 Cov.: 70 AF XY: 0.0000415 AC XY: 3 AN XY: 72348

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000247 AC: 1 AN: 40532

American (AMR) AF: 0.00 AC: 0 AN: 14838

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3396

East Asian (EAS) AF: 0.000199 AC: 1 AN: 5020

South Asian (SAS) AF: 0.000216 AC: 1 AN: 4628

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10290

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 278

European-Non Finnish (NFE) AF: 0.0000453 AC: 3 AN: 66210

Other (OTH) AF: 0.00 AC: 0 AN: 2050

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.45
PhyloP100		-0.94

Splicing

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

Other links and lift over

dbSNP: rs7589328; hg19: chr2-114340628;