14-101056219-T-C

Variant names:

• chr14-101056219-T-C
• rs56103835
• ENST00000385269.2:n.1T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000385269.2(MIR323B):​n.1T>C 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 0.246 in 532,696 control chromosomes in the GnomAD database, including 20,747 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 0.19 (4156 hom., cov: 32)
  • Exomes 𝑓: 0.27 (16591 hom.)
• Consequence: MIR323B ENST00000385269.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.212
• Publications: 41 publications found

Genes affected

MIR323B (HGNC:38349): (microRNA 323b) 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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIR323B	NR_036133.1	n.1T>C		non_coding_transcript_exon_variant	Exon 1 of 1
MIR323B	unassigned_transcript_2435	n.-14T>C		upstream_gene_variant
MIR323B	unassigned_transcript_2436	n.-50T>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIR323B	ENST00000385269.2	n.1T>C		non_coding_transcript_exon_variant	Exon 1 of 1	6
MEG9	ENST00000699460.1	n.2751T>C		non_coding_transcript_exon_variant	Exon 17 of 17
MEG9	ENST00000699461.1	n.356T>C		non_coding_transcript_exon_variant	Exon 3 of 7

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29390 AN: 152090 Hom.: 4157 Cov.: 32

Gnomad AFR AF: 0.0507

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.683

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.211

GnomAD2 exomes AF: 0.278 AC: 69625 AN: 250342 AF XY: 0.277

Gnomad AFR exome AF: 0.0473

Gnomad AMR exome AF: 0.441

Gnomad ASJ exome AF: 0.184

Gnomad EAS exome AF: 0.678

Gnomad FIN exome AF: 0.203

Gnomad NFE exome AF: 0.202

Gnomad OTH exome AF: 0.242

GnomAD4 exome AF: 0.267 AC: 101402 AN: 380488 Hom.: 16591 Cov.: 0 AF XY: 0.270 AC XY: 58460 AN XY: 216726

African (AFR) AF: 0.0494 AC: 516 AN: 10448

American (AMR) AF: 0.443 AC: 16066 AN: 36238

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 2140 AN: 11738

East Asian (EAS) AF: 0.693 AC: 9099 AN: 13130

South Asian (SAS) AF: 0.343 AC: 22846 AN: 66612

European-Finnish (FIN) AF: 0.202 AC: 6533 AN: 32308

Middle Eastern (MID) AF: 0.210 AC: 331 AN: 1576

European-Non Finnish (NFE) AF: 0.209 AC: 40130 AN: 191866

Other (OTH) AF: 0.226 AC: 3741 AN: 16572

GnomAD4 genome AF: 0.193 AC: 29393 AN: 152208 Hom.: 4156 Cov.: 32 AF XY: 0.202 AC XY: 15040 AN XY: 74394

African (AFR) AF: 0.0505 AC: 2101 AN: 41568

American (AMR) AF: 0.304 AC: 4644 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 639 AN: 3470

East Asian (EAS) AF: 0.684 AC: 3526 AN: 5156

South Asian (SAS) AF: 0.365 AC: 1757 AN: 4820

European-Finnish (FIN) AF: 0.200 AC: 2122 AN: 10594

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.205 AC: 13941 AN: 67998

Other (OTH) AF: 0.212 AC: 449 AN: 2114

Alfa AF: 0.203 Hom.: 7102

Bravo AF: 0.197

Asia WGS AF: 0.466 AC: 1620 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.4
DANN	Benign	0.59
PhyloP100		-0.21

Splicing

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

Other links and lift over

dbSNP: rs56103835; hg19: chr14-101522556;