chr16-2271814-GC-G

Variant names:

• chr16-2271814-GC-G
• rs35356504
• ENST00000401276.3:n.73delC

Variant summary

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

The ENST00000401276.3(MIR940):​n.73delC 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 0.00000268 in 373,276 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: MIR940 ENST00000401276.3 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.471
• Publications: 4 publications found

Genes affected

MIR940 (HGNC:33683): (microRNA 940) 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]

MIR3677HG (HGNC:55382): (MIR3677 and MIR940 host gene)

ACMG classification

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

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000401276.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR940	NR_030636.1		n.73delC		non_coding_transcript_exon	Exon 1 of 1
	MIR3677HG	NR_132988.1		n.325delC		non_coding_transcript_exon	Exon 2 of 3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR940	ENST00000401276.3	TSL:6	n.73delC		non_coding_transcript_exon	Exon 1 of 1
	MIR3677HG	ENST00000562838.2	TSL:2	n.514delC		non_coding_transcript_exon	Exon 2 of 3
	MIR3677HG	ENST00000762695.1		n.253delC		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000268 AC: 1 AN: 373276 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 213310

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

African (AFR) AF: 0.00 AC: 0 AN: 10160

American (AMR) AF: 0.0000287 AC: 1 AN: 34790

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11472

East Asian (EAS) AF: 0.00 AC: 0 AN: 12860

South Asian (SAS) AF: 0.00 AC: 0 AN: 66218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28854

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2816

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 189794

Other (OTH) AF: 0.00 AC: 0 AN: 16312

⚠️ 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 Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.47

Splicing

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

Other links and lift over

dbSNP: rs35356504; hg19: chr16-2321815;