rs33982250

Variant names:

• chr5-154685822-TAA-T
• rs33982250
• ENST00000408625.1:n.49_50delAA

Your query was ambiguous. Multiple possible variants found:

• chr5-154685822-TAA-T
• chr5-154685822-TAA-TA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000408625.1(MIR1303):​n.49_50delAA variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 323,106 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000015 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MIR1303 ENST00000408625.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347
• Publications: 6 publications found

Genes affected

MIR1303 (HGNC:35301): (microRNA 1303) 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]

LARP1 (HGNC:29531): (La ribonucleoprotein 1, translational regulator) Enables eukaryotic initiation factor 4E binding activity; nucleic acid binding activity; and ribosomal small subunit binding activity. Involved in several processes, including TORC1 signaling; cellular response to rapamycin; and posttranscriptional regulation of gene expression. Located in cytoplasmic stress granule. Colocalizes with TORC1 complex and polysomal ribosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIR1303	NR_031638.1	n.49_50delAA		non_coding_transcript_exon_variant	Exon 1 of 1
LARP1	NM_001367713.1	c.-180+2787_-180+2788delAA		intron_variant	Intron 1 of 18		NP_001354642.1
LARP1	NM_001367714.1	c.-297+2787_-297+2788delAA		intron_variant	Intron 1 of 19		NP_001354643.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIR1303	ENST00000408625.1	n.49_50delAA		non_coding_transcript_exon_variant	Exon 1 of 1	6
LARP1	ENST00000687700.1	c.-180+2787_-180+2788delAA		intron_variant	Intron 1 of 18			ENSP00000508958.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 149290 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000110 AC: 2 AN: 182604 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: 0.0000788

Gnomad FIN exome AF: 0.0000966

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000155 AC: 5 AN: 323106 Hom.: 0 AF XY: 0.00000537 AC XY: 1 AN XY: 186364

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

African (AFR) AF: 0.000130 AC: 1 AN: 7710

American (AMR) AF: 0.0000642 AC: 2 AN: 31140

Ashkenazi Jewish (ASJ) AF: 0.0000952 AC: 1 AN: 10508

East Asian (EAS) AF: 0.00 AC: 0 AN: 11282

South Asian (SAS) AF: 0.00 AC: 0 AN: 59138

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 15078

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2630

European-Non Finnish (NFE) AF: 0.00000585 AC: 1 AN: 170986

Other (OTH) AF: 0.00 AC: 0 AN: 14634

⚠️ 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: AC0 AF: 0.00 AC: 0 AN: 149290 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 72712

African (AFR) AF: 0.00 AC: 0 AN: 40240

American (AMR) AF: 0.00 AC: 0 AN: 15054

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3454

East Asian (EAS) AF: 0.00 AC: 0 AN: 5090

South Asian (SAS) AF: 0.00 AC: 0 AN: 4746

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10044

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67402

Other (OTH) AF: 0.00 AC: 0 AN: 2046

Alfa AF: 0.00 Hom.: 999

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.35

Splicing

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

Other links and lift over

dbSNP: rs33982250; hg19: chr5-154065382;