rs8011440

Positions:

• chr14-101558821-C-T

Variant summary

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

The ENST00000554441.7(DIO3OS):​n.452G>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 0.411 in 242,610 control chromosomes in the GnomAD database, including 20,981 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 0.42 (13208 hom., cov: 31)
  • Exomes 𝑓: 0.40 (7773 hom.)
• Consequence: DIO3OS ENST00000554441.7 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.389

Genes affected

DIO3OS (HGNC:20348): (DIO3 opposite strand upstream RNA) The mouse and human DIO3OS and DIO3 (MIM 601038) genes overlap and are transcribed in opposite directions. The mouse Dio3 gene is imprinted from the paternal allele during fetal development, suggesting that DIO3OS is a noncoding gene that may have a role in maintaining monoallelic expression of DIO3 (Hernandez et al., 2004 [PubMed 14962667]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIO3OS	NR_152588.1	n.171+1431G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DIO3OS	ENST00000700197.1	n.1142G>A		non_coding_transcript_exon_variant	8/9

Frequencies

GnomAD3 genomes AF: 0.416 AC: 63054 AN: 151468 Hom.: 13192 Cov.: 31

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.511

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.420

GnomAD4 exome AF: 0.402 AC: 36622 AN: 91024 Hom.: 7773 Cov.: 0 AF XY: 0.407 AC XY: 19223 AN XY: 47252

Gnomad4 AFR exome AF: 0.409

Gnomad4 AMR exome AF: 0.415

Gnomad4 ASJ exome AF: 0.323

Gnomad4 EAS exome AF: 0.506

Gnomad4 SAS exome AF: 0.448

Gnomad4 FIN exome AF: 0.394

Gnomad4 NFE exome AF: 0.385

Gnomad4 OTH exome AF: 0.397

GnomAD4 genome AF: 0.416 AC: 63118 AN: 151586 Hom.: 13208 Cov.: 31 AF XY: 0.418 AC XY: 30965 AN XY: 74070

Gnomad4 AFR AF: 0.427

Gnomad4 AMR AF: 0.394

Gnomad4 ASJ AF: 0.340

Gnomad4 EAS AF: 0.511

Gnomad4 SAS AF: 0.484

Gnomad4 FIN AF: 0.434

Gnomad4 NFE AF: 0.402

Gnomad4 OTH AF: 0.426

Alfa AF: 0.411 Hom.: 5229

Bravo AF: 0.413

Asia WGS AF: 0.507 AC: 1764 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.34
DANN	Benign	0.15

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8011440; hg19: chr14-102025158;