2-113583051-C-T

Variant names:

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

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>A 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 0.29 (0 hom., cov: 70)
  • Exomes 𝑓: 0.15 (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=-0.9).

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.286 AC: 29328 AN: 102706 Hom.: 0 Cov.: 70

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.337

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.283

GnomAD2 exomes AF: 0.0408 AC: 6560 AN: 160910 AF XY: 0.0402

Gnomad AFR exome AF: 0.0870

Gnomad AMR exome AF: 0.0339

Gnomad ASJ exome AF: 0.0710

Gnomad EAS exome AF: 0.0661

Gnomad FIN exome AF: 0.0307

Gnomad NFE exome AF: 0.0278

Gnomad OTH exome AF: 0.0457

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.146 AC: 29225 AN: 200520 Hom.: 0 Cov.: 0 AF XY: 0.149 AC XY: 17092 AN XY: 114662

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

African (AFR) AF: 0.260 AC: 1257 AN: 4832

American (AMR) AF: 0.109 AC: 1963 AN: 17992

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 1010 AN: 5914

East Asian (EAS) AF: 0.219 AC: 1353 AN: 6186

South Asian (SAS) AF: 0.187 AC: 6670 AN: 35632

European-Finnish (FIN) AF: 0.115 AC: 1844 AN: 16002

Middle Eastern (MID) AF: 0.218 AC: 141 AN: 648

European-Non Finnish (NFE) AF: 0.131 AC: 13688 AN: 104564

Other (OTH) AF: 0.148 AC: 1299 AN: 8750

⚠️ 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: InbreedingCoeff AF: 0.286 AC: 29361 AN: 102784 Hom.: 0 Cov.: 70 AF XY: 0.284 AC XY: 14224 AN XY: 50138

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

African (AFR) AF: 0.381 AC: 10674 AN: 28026

American (AMR) AF: 0.263 AC: 2663 AN: 10130

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 676 AN: 2386

East Asian (EAS) AF: 0.337 AC: 1137 AN: 3372

South Asian (SAS) AF: 0.275 AC: 936 AN: 3406

European-Finnish (FIN) AF: 0.209 AC: 1462 AN: 6992

Middle Eastern (MID) AF: 0.315 AC: 58 AN: 184

European-Non Finnish (NFE) AF: 0.241 AC: 11136 AN: 46206

Other (OTH) AF: 0.279 AC: 402 AN: 1440

⚠️ 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: 0.182 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.1
DANN	Benign	0.73
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; COSMIC: COSV58538713;