ENST00000692840.2:n.841G>T

Variant names:

• chr6-33207798-C-A
• rs107822
• ENST00000692840.2:n.841G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000692840.2(ENSG00000288751):​n.841G>T 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 0.00000341 in 293,106 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: ENSG00000288751 ENST00000692840.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00200
• Publications: 0 publications found

Genes affected

ENSG00000288751 (HGNC:):

MIR219A1 (HGNC:31597): (microRNA 219a-1) 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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIR219A1	NR_029633.1	n.-37C>A		upstream_gene_variant
MIR219A1	unassigned_transcript_1108	n.-57C>A		upstream_gene_variant
MIR219A1	unassigned_transcript_1109	n.-98C>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000288751	ENST00000692840.2	n.841G>T		non_coding_transcript_exon_variant	Exon 1 of 1
ENSG00000306895	ENST00000821858.1	n.850C>A		non_coding_transcript_exon_variant	Exon 1 of 1
MIR219A1	ENST00000362166.1	n.-37C>A		upstream_gene_variant		6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000341 AC: 1 AN: 293106 Hom.: 0 Cov.: 0 AF XY: 0.00000595 AC XY: 1 AN XY: 167980

⚠️ 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: 8458

American (AMR) AF: 0.0000397 AC: 1 AN: 25202

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9324

East Asian (EAS) AF: 0.00 AC: 0 AN: 9448

South Asian (SAS) AF: 0.00 AC: 0 AN: 56320

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27462

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2642

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 141568

Other (OTH) AF: 0.00 AC: 0 AN: 12682

⚠️ 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.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	13
DANN	Benign	0.70
PhyloP100		0.0020

Splicing

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

Other links and lift over

dbSNP: rs107822; hg19: chr6-33175575;