rs41286570

Positions:

• chr14-101059790-G-A
• chr14-101059790-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NR_029704.1(MIR154):​n.36G>A 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 0.000593 in 534,756 control chromosomes in the GnomAD database, including 2 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 0.00085 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00049 (1 hom.)
• Consequence: MIR154 NR_029704.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0120

Genes affected

MIR154 (HGNC:31541): (microRNA 154) 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]

MEG9 (HGNC:43874): (maternally expressed 9)

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MIR154	NR_029704.1	n.36G>A		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIR154	ENST00000385243.1	n.36G>A		mature_miRNA_variant	1/1
MEG9	ENST00000699461.1	n.382-1703G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.000848 AC: 129 AN: 152174 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

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: 0.00129

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000446 AC: 112 AN: 251030 Hom.: 0 AF XY: 0.000412 AC XY: 56 AN XY: 135894

Gnomad AFR exome AF: 0.0000617

Gnomad AMR exome AF: 0.000318

Gnomad ASJ exome AF: 0.0000995

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000820

Gnomad OTH exome AF: 0.000652

GnomAD4 exome AF: 0.000492 AC: 188 AN: 382464 Hom.: 1 Cov.: 0 AF XY: 0.000446 AC XY: 97 AN XY: 217730

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000303

Gnomad4 ASJ exome AF: 0.0000851

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000749

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000812

Gnomad4 OTH exome AF: 0.000897

GnomAD4 genome AF: 0.000847 AC: 129 AN: 152292 Hom.: 1 Cov.: 33 AF XY: 0.000913 AC XY: 68 AN XY: 74476

Gnomad4 AFR AF: 0.000192

Gnomad4 AMR AF: 0.00216

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00129

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000683 Hom.: 0

Bravo AF: 0.000737

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	17
DANN	Benign	0.91

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs41286570; hg19: chr14-101526127; COSMIC: COSV62998830;