8-128008933-G-A

Position:

• chr8-128008933-G-A

Variant summary

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

The NR_031611.1(MIR1206):​n.36G>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 0.619 in 522,284 control chromosomes in the GnomAD database, including 101,439 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 0.65 (32173 hom., cov: 32)
  • Exomes 𝑓: 0.61 (69266 hom.)
• Consequence: MIR1206 NR_031611.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.334

Genes affected

MIR1206 (HGNC:35272): (microRNA 1206) 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MIR1206	NR_031611.1	n.36G>A		non_coding_transcript_exon_variant	1/1
PVT1	NR_003367.3	n.1212+19642G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIR1206	ENST00000637127.1	n.36G>A		non_coding_transcript_exon_variant	1/1
PVT1	ENST00000651587.1	n.912+19642G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.647 AC: 98203 AN: 151886 Hom.: 32136 Cov.: 32

Gnomad AFR AF: 0.728

Gnomad AMI AF: 0.682

Gnomad AMR AF: 0.669

Gnomad ASJ AF: 0.585

Gnomad EAS AF: 0.713

Gnomad SAS AF: 0.554

Gnomad FIN AF: 0.638

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.624

GnomAD3 exomes AF: 0.626 AC: 154054 AN: 246132 Hom.: 48779 AF XY: 0.616 AC XY: 82592 AN XY: 134010

Gnomad AFR exome AF: 0.731

Gnomad AMR exome AF: 0.697

Gnomad ASJ exome AF: 0.606

Gnomad EAS exome AF: 0.710

Gnomad SAS exome AF: 0.528

Gnomad FIN exome AF: 0.642

Gnomad NFE exome AF: 0.603

Gnomad OTH exome AF: 0.596

GnomAD4 exome AF: 0.608 AC: 225148 AN: 370280 Hom.: 69266 Cov.: 0 AF XY: 0.599 AC XY: 126400 AN XY: 211028

Gnomad4 AFR exome AF: 0.725

Gnomad4 AMR exome AF: 0.695

Gnomad4 ASJ exome AF: 0.605

Gnomad4 EAS exome AF: 0.711

Gnomad4 SAS exome AF: 0.532

Gnomad4 FIN exome AF: 0.644

Gnomad4 NFE exome AF: 0.600

Gnomad4 OTH exome AF: 0.600

GnomAD4 genome AF: 0.647 AC: 98287 AN: 152004 Hom.: 32173 Cov.: 32 AF XY: 0.649 AC XY: 48231 AN XY: 74298

Gnomad4 AFR AF: 0.729

Gnomad4 AMR AF: 0.669

Gnomad4 ASJ AF: 0.585

Gnomad4 EAS AF: 0.713

Gnomad4 SAS AF: 0.554

Gnomad4 FIN AF: 0.638

Gnomad4 NFE AF: 0.598

Gnomad4 OTH AF: 0.619

Alfa AF: 0.623 Hom.: 18721

Bravo AF: 0.657

Asia WGS AF: 0.593 AC: 2062 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.7
DANN	Benign	0.76

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2114358; hg19: chr8-129021179;