8-128150187-G-C

Variant names:

• chr8-128150187-G-C
• rs2648841
• ENST00000408334.1:n.72G>C

Variant summary

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

The ENST00000408334.1(MIR1208):​n.72G>C variant causes a splice region, non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000279 in 358,726 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: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: MIR1208 ENST00000408334.1 splice_region, non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365
• Publications: 20 publications found

Genes affected

MIR1208 (HGNC:35274): (microRNA 1208) 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]

PVT1 (HGNC:9709): (Pvt1 oncogene) This gene represents a long non-coding RNA locus that has been identified as a candidate oncogene. Increased copy number and overexpression of this gene are associated with many types of cancers including breast and ovarian cancers, acute myeloid leukemia and Hodgkin lymphoma. Allelic variants of this gene are also associated with end-stage renal disease attributed to type 1 diabetes. Consistent with its association with various types of cancer, transcription of this gene is regulated by the tumor suppressor p53 through a canonical p53-binding site, and it has been implicated in regulating levels of the proto-oncogene MYC to promote tumorigenesis. [provided by RefSeq, Sep 2015]

ENSG00000309955 (HGNC:):

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=-0.89).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000408334.1. 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
	MIR1208	NR_031613.1		n.72G>C		splice_region non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIR1208	ENST00000408334.1	TSL:6	n.72G>C		splice_region non_coding_transcript_exon	Exon 1 of 1
	PVT1	ENST00000650846.1		n.403+2199G>C		intron	N/A
	PVT1	ENST00000651587.1		n.1378+2199G>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000279 AC: 1 AN: 358726 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 205844

African (AFR) AF: 0.00 AC: 0 AN: 8698

American (AMR) AF: 0.00 AC: 0 AN: 31900

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11218

East Asian (EAS) AF: 0.00 AC: 0 AN: 10290

South Asian (SAS) AF: 0.00 AC: 0 AN: 63246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32040

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2790

European-Non Finnish (NFE) AF: 0.00000547 AC: 1 AN: 182840

Other (OTH) AF: 0.00 AC: 0 AN: 15704

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 61

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.79
DANN	Benign	0.45
PhyloP100		0.36

Splicing

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

Other links and lift over

dbSNP: rs2648841; hg19: chr8-129162433;