rs2648841

Positions:

• chr8-128150187-G-A
• chr8-128150187-G-C
• chr8-128150187-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_031613.1(MIR1208):​n.72G>A 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 0.0417 in 510,780 control chromosomes in the GnomAD database, including 726 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 0.048 (267 hom., cov: 32)
  • Exomes 𝑓: 0.039 (459 hom.)
• Consequence: MIR1208 NR_031613.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0937 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MIR1208	NR_031613.1	n.72G>A		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIR1208	ENST00000408334.1	n.72G>A		non_coding_transcript_exon_variant	1/1
PVT1	ENST00000651587.1	n.1378+2199G>A		intron_variant, non_coding_transcript_variant
PVT1	ENST00000650846.1	n.403+2199G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0478 AC: 7263 AN: 152004 Hom.: 261 Cov.: 32

Gnomad AFR AF: 0.0956

Gnomad AMI AF: 0.0385

Gnomad AMR AF: 0.0467

Gnomad ASJ AF: 0.0536

Gnomad EAS AF: 0.0540

Gnomad SAS AF: 0.0714

Gnomad FIN AF: 0.0287

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0198

Gnomad OTH AF: 0.0407

GnomAD3 exomes AF: 0.0422 AC: 9315 AN: 220756 Hom.: 299 AF XY: 0.0420 AC XY: 5100 AN XY: 121546

Gnomad AFR exome AF: 0.102

Gnomad AMR exome AF: 0.0689

Gnomad ASJ exome AF: 0.0422

Gnomad EAS exome AF: 0.0516

Gnomad SAS exome AF: 0.0764

Gnomad FIN exome AF: 0.0253

Gnomad NFE exome AF: 0.0197

Gnomad OTH exome AF: 0.0430

GnomAD4 exome AF: 0.0391 AC: 14020 AN: 358658 Hom.: 459 Cov.: 0 AF XY: 0.0410 AC XY: 8442 AN XY: 205804

Gnomad4 AFR exome AF: 0.0989

Gnomad4 AMR exome AF: 0.0679

Gnomad4 ASJ exome AF: 0.0420

Gnomad4 EAS exome AF: 0.0586

Gnomad4 SAS exome AF: 0.0753

Gnomad4 FIN exome AF: 0.0257

Gnomad4 NFE exome AF: 0.0199

Gnomad4 OTH exome AF: 0.0366

GnomAD4 genome AF: 0.0480 AC: 7299 AN: 152122 Hom.: 267 Cov.: 32 AF XY: 0.0478 AC XY: 3554 AN XY: 74358

Gnomad4 AFR AF: 0.0961

Gnomad4 AMR AF: 0.0466

Gnomad4 ASJ AF: 0.0536

Gnomad4 EAS AF: 0.0543

Gnomad4 SAS AF: 0.0717

Gnomad4 FIN AF: 0.0287

Gnomad4 NFE AF: 0.0198

Gnomad4 OTH AF: 0.0408

Alfa AF: 0.0180 Hom.: 59

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.1
DANN	Benign	0.49

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2648841; hg19: chr8-129162433;