8-128150187-G-T

Variant names:

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

Variant summary

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

The ENST00000408334.1(MIR1208):​n.72G>T 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 0.121 in 510,642 control chromosomes in the GnomAD database, including 5,359 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 0.11 (1250 hom., cov: 32)
  • Exomes 𝑓: 0.13 (4109 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

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>T		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>T		splice_region non_coding_transcript_exon	Exon 1 of 1
	PVT1	ENST00000650846.1		n.403+2199G>T		intron	N/A
	PVT1	ENST00000651587.1		n.1378+2199G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16432 AN: 151982 Hom.: 1256 Cov.: 32

Gnomad AFR AF: 0.0781

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.0654

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0849

Gnomad OTH AF: 0.121

GnomAD2 exomes AF: 0.141 AC: 31193 AN: 220756 AF XY: 0.137

Gnomad AFR exome AF: 0.0791

Gnomad AMR exome AF: 0.235

Gnomad ASJ exome AF: 0.0551

Gnomad EAS exome AF: 0.420

Gnomad FIN exome AF: 0.112

Gnomad NFE exome AF: 0.0852

Gnomad OTH exome AF: 0.112

GnomAD4 exome AF: 0.127 AC: 45365 AN: 358542 Hom.: 4109 Cov.: 0 AF XY: 0.129 AC XY: 26489 AN XY: 205748

African (AFR) AF: 0.0724 AC: 629 AN: 8690

American (AMR) AF: 0.229 AC: 7305 AN: 31846

Ashkenazi Jewish (ASJ) AF: 0.0557 AC: 625 AN: 11214

East Asian (EAS) AF: 0.419 AC: 4303 AN: 10270

South Asian (SAS) AF: 0.186 AC: 11745 AN: 63204

European-Finnish (FIN) AF: 0.107 AC: 3420 AN: 32036

Middle Eastern (MID) AF: 0.0638 AC: 178 AN: 2790

European-Non Finnish (NFE) AF: 0.0841 AC: 15382 AN: 182794

Other (OTH) AF: 0.113 AC: 1778 AN: 15698

GnomAD4 genome AF: 0.108 AC: 16433 AN: 152100 Hom.: 1250 Cov.: 32 AF XY: 0.114 AC XY: 8449 AN XY: 74342

African (AFR) AF: 0.0783 AC: 3247 AN: 41492

American (AMR) AF: 0.156 AC: 2389 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0654 AC: 227 AN: 3470

East Asian (EAS) AF: 0.429 AC: 2220 AN: 5174

South Asian (SAS) AF: 0.196 AC: 942 AN: 4810

European-Finnish (FIN) AF: 0.116 AC: 1231 AN: 10576

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0849 AC: 5774 AN: 67982

Other (OTH) AF: 0.120 AC: 254 AN: 2110

Alfa AF: 0.0485 Hom.: 61

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.81
DANN	Benign	0.51
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;