rs8011440

Variant names:

• chr14-101558821-C-T
• rs8011440
• ENST00000554441.8:n.480G>A

Variant summary

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

The ENST00000554441.8(DIO3OS):​n.480G>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 ENST00000554441.8 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.389
• Publications: 2 publications found

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000554441.8. 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
	DIO3OS	NR_152589.1		n.185G>A		non_coding_transcript_exon	Exon 2 of 4
	DIO3OS	NR_152590.1		n.185G>A		non_coding_transcript_exon	Exon 2 of 2
	DIO3OS	NR_152591.1		n.185G>A		non_coding_transcript_exon	Exon 2 of 3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIO3OS	ENST00000554441.8	TSL:1	n.480G>A		non_coding_transcript_exon	Exon 3 of 4
	DIO3OS	ENST00000554694.3	TSL:1	n.245G>A		non_coding_transcript_exon	Exon 2 of 3
	DIO3OS	ENST00000555174.7	TSL:1	n.194G>A		non_coding_transcript_exon	Exon 2 of 2

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

African (AFR) AF: 0.409 AC: 1404 AN: 3430

American (AMR) AF: 0.415 AC: 2252 AN: 5430

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 707 AN: 2188

East Asian (EAS) AF: 0.506 AC: 2549 AN: 5040

South Asian (SAS) AF: 0.448 AC: 5500 AN: 12284

European-Finnish (FIN) AF: 0.394 AC: 1534 AN: 3898

Middle Eastern (MID) AF: 0.394 AC: 148 AN: 376

European-Non Finnish (NFE) AF: 0.385 AC: 20587 AN: 53486

Other (OTH) AF: 0.397 AC: 1941 AN: 4892

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

African (AFR) AF: 0.427 AC: 17607 AN: 41262

American (AMR) AF: 0.394 AC: 6004 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 1180 AN: 3468

East Asian (EAS) AF: 0.511 AC: 2609 AN: 5106

South Asian (SAS) AF: 0.484 AC: 2332 AN: 4814

European-Finnish (FIN) AF: 0.434 AC: 4573 AN: 10540

Middle Eastern (MID) AF: 0.497 AC: 142 AN: 286

European-Non Finnish (NFE) AF: 0.402 AC: 27305 AN: 67850

Other (OTH) AF: 0.426 AC: 897 AN: 2106

Alfa AF: 0.409 Hom.: 10057

Bravo AF: 0.413

Asia WGS AF: 0.507 AC: 1764 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.34
DANN	Benign	0.15
PhyloP100		-0.39

Splicing

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

Other links and lift over

dbSNP: rs8011440; hg19: chr14-102025158;