rs11205415

chr1-248826485-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The 1-248826485-T-G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 154,760 control chromosomes in the GnomAD database, including 8,558 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 0.25 (8499 hom., cov: 32)
  • Exomes 𝑓: 0.19 (59 hom.)
• Consequence: MIR3124 NR_036070.1 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.865

Genes affected

MIR3124 (HGNC:38262): (microRNA 3124) 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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MIR3124	NR_036070.1			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIR3124	ENST00000582636.1			downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37857 AN: 152024 Hom.: 8477 Cov.: 32

Gnomad AFR AF: 0.572

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.0992

Gnomad EAS AF: 0.534

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.0823

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.0828

Gnomad OTH AF: 0.202

GnomAD3 exomes AF: 0.128 AC: 842 AN: 6578 Hom.: 118 AF XY: 0.104 AC XY: 332 AN XY: 3198

Gnomad AFR exome AF: 0.616

Gnomad AMR exome AF: 0.246

Gnomad ASJ exome AF: 0.0931

Gnomad EAS exome AF: 0.600

Gnomad SAS exome AF: 0.241

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0859

Gnomad OTH exome AF: 0.190

GnomAD4 exome AF: 0.194 AC: 509 AN: 2618 Hom.: 59 Cov.: 0 AF XY: 0.186 AC XY: 251 AN XY: 1346

Gnomad4 AFR exome AF: 0.486

Gnomad4 AMR exome AF: 0.750

Gnomad4 ASJ exome AF: 0.00

Gnomad4 SAS exome AF: 0.196

Gnomad4 FIN exome AF: 0.0701

Gnomad4 NFE exome AF: 0.0798

Gnomad4 OTH exome AF: 0.345

GnomAD4 genome AF: 0.249 AC: 37929 AN: 152142 Hom.: 8499 Cov.: 32 AF XY: 0.251 AC XY: 18656 AN XY: 74402

Gnomad4 AFR AF: 0.572

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.0992

Gnomad4 EAS AF: 0.534

Gnomad4 SAS AF: 0.289

Gnomad4 FIN AF: 0.0823

Gnomad4 NFE AF: 0.0828

Gnomad4 OTH AF: 0.202

Alfa AF: 0.146 Hom.: 2008

Bravo AF: 0.273

Asia WGS AF: 0.441 AC: 1528 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	3.8
Dann	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs11205415; hg19: chr1-249120684; COSMIC: COSV63539586; COSMIC: COSV63539586;