rs11844707

chr14-101044276-G-Achr14-101044276-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NR_031571.1(MIR1185-2):n.79G>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 0.0173 in 534,246 control chromosomes in the GnomAD database, including 649 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 0.045 (509 hom., cov: 33)
  • Exomes 𝑓: 0.0062 (140 hom.)
• Consequence: MIR1185-2 NR_031571.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0310

Genes affected

MIR1185-2 (HGNC:35254): (microRNA 1185-2) 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 Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MIR1185-2	NR_031571.1	n.79G>A		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIR1185-2	ENST00000408687.1	n.79G>A		non_coding_transcript_exon_variant	1/1
MEG9	ENST00000699460.1	n.627-45G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0451 AC: 6871 AN: 152186 Hom.: 506 Cov.: 33

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0167

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000838

Gnomad OTH AF: 0.0315

GnomAD3 exomes AF: 0.0116 AC: 2857 AN: 245338 Hom.: 208 AF XY: 0.00877 AC XY: 1173 AN XY: 133768

Gnomad AFR exome AF: 0.158

Gnomad AMR exome AF: 0.00935

Gnomad ASJ exome AF: 0.00151

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000295

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000874

Gnomad OTH exome AF: 0.00597

GnomAD4 exome AF: 0.00618 AC: 2360 AN: 381942 Hom.: 140 Cov.: 0 AF XY: 0.00467 AC XY: 1016 AN XY: 217406

Gnomad4 AFR exome AF: 0.158

Gnomad4 AMR exome AF: 0.00965

Gnomad4 ASJ exome AF: 0.00137

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000315

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000630

Gnomad4 OTH exome AF: 0.00958

GnomAD4 genome AF: 0.0452 AC: 6887 AN: 152304 Hom.: 509 Cov.: 33 AF XY: 0.0445 AC XY: 3311 AN XY: 74480

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.0167

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000838

Gnomad4 OTH AF: 0.0312

Alfa AF: 0.0202 Hom.: 74

Bravo AF: 0.0511

Asia WGS AF: 0.0120 AC: 41 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
Cadd	Benign	16
Dann	Benign	0.89

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11844707; hg19: chr14-101510613; COSMIC: COSV62999882;