rs1190716

Variant names:

• chr14-101558887-C-T
• rs1190716
• ENST00000554441.7:n.439-53G>A

Variant summary

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

The ENST00000700222.1(DIO3OS):​n.1468G>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 0.133 in 213,384 control chromosomes in the GnomAD database, including 2,612 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 0.15 (2229 hom., cov: 32)
  • Exomes 𝑓: 0.091 (383 hom.)
• Consequence: DIO3OS ENST00000700222.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIO3OS	NR_152588.1	n.171+1365G>A		intron_variant	Intron 1 of 1
DIO3OS	NR_152589.1	n.172-53G>A		intron_variant	Intron 1 of 3
DIO3OS	NR_152590.1	n.172-53G>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIO3OS	ENST00000554441.7	n.439-53G>A		intron_variant	Intron 2 of 3	1
DIO3OS	ENST00000554694.3	n.232-53G>A		intron_variant	Intron 1 of 2	1
DIO3OS	ENST00000555174.6	n.178-53G>A		intron_variant	Intron 1 of 1	1

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22534 AN: 149474 Hom.: 2223 Cov.: 32

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.0465

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.0855

Gnomad EAS AF: 0.00692

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.0716

Gnomad MID AF: 0.115

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.129

GnomAD4 exome AF: 0.0911 AC: 5809 AN: 63792 Hom.: 383 Cov.: 0 AF XY: 0.0893 AC XY: 2947 AN XY: 32994

Gnomad4 AFR exome AF: 0.249 AC: 563 AN: 2264

Gnomad4 AMR exome AF: 0.0788 AC: 329 AN: 4174

Gnomad4 ASJ exome AF: 0.0714 AC: 109 AN: 1526

Gnomad4 EAS exome AF: 0.00563 AC: 21 AN: 3732

Gnomad4 SAS exome AF: 0.0907 AC: 629 AN: 6936

Gnomad4 FIN exome AF: 0.0626 AC: 151 AN: 2412

Gnomad4 NFE exome AF: 0.0935 AC: 3643 AN: 38972

Gnomad4 Remaining exome AF: 0.0946 AC: 332 AN: 3510

GnomAD4 genome AF: 0.151 AC: 22580 AN: 149592 Hom.: 2229 Cov.: 32 AF XY: 0.146 AC XY: 10616 AN XY: 72924

Gnomad4 AFR AF: 0.289 AC: 0.289487 AN: 0.289487

Gnomad4 AMR AF: 0.114 AC: 0.114351 AN: 0.114351

Gnomad4 ASJ AF: 0.0855 AC: 0.0855491 AN: 0.0855491

Gnomad4 EAS AF: 0.00713 AC: 0.00713154 AN: 0.00713154

Gnomad4 SAS AF: 0.108 AC: 0.108219 AN: 0.108219

Gnomad4 FIN AF: 0.0716 AC: 0.0715664 AN: 0.0715664

Gnomad4 NFE AF: 0.108 AC: 0.107941 AN: 0.107941

Gnomad4 OTH AF: 0.128 AC: 0.127751 AN: 0.127751

Alfa AF: 0.117 Hom.: 1689

Bravo AF: 0.157

Asia WGS AF: 0.0790 AC: 276 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.4
DANN	Benign	0.67

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1190716; hg19: chr14-102025224;