Genetic Variant DIO3OS:n.169+3510A>G (chr14-101556742-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000557109.6(DIO3OS):n.169+3510A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 151,974 control chromosomes in the GnomAD database, including 26,425 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 0.57 ( 26425 hom., cov: 32)

Consequence

DIO3OS
ENST00000557109.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.205

Variant links:

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]

DIO3OS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.772 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIO3OS	NR_152588.1 link	n.171+3510A>G		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
DIO3OS	ENST00000557109.6 link	n.169+3510A>G	intron_variant	Intron 1 of 1	1
DIO3OS	ENST00000700216.1 link	n.123-1066A>G	intron_variant	Intron 1 of 2
DIO3OS	ENST00000700217.1 link	n.370-1066A>G	intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes

AF:

0.574

AC:

87190

AN:

151856

Hom.:

26370

Cov.:

show subpopulations

Gnomad AFR

AF:

0.779

Gnomad AMI

AF:

0.471

Gnomad AMR

AF:

0.480

Gnomad ASJ

AF:

0.401

Gnomad EAS

AF:

0.518

Gnomad SAS

AF:

0.566

Gnomad FIN

AF:

0.519

Gnomad MID

AF:

0.592

Gnomad NFE

AF:

0.495

Gnomad OTH

AF:

0.542

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.575

AC:

87309

AN:

151974

Hom.:

26425

Cov.:

AF XY:

0.570

AC XY:

42319

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.779

Gnomad4 AMR

AF:

0.480

Gnomad4 ASJ

AF:

0.401

Gnomad4 EAS

AF:

0.519

Gnomad4 SAS

AF:

0.566

Gnomad4 FIN

AF:

0.519

Gnomad4 NFE

AF:

0.495

Gnomad4 OTH

AF:

0.547

Alfa

AF:

0.500

Hom.:

15924

Bravo

AF:

0.577

Asia WGS

AF:

0.575

AC:

2002

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

6.3

DANN

Benign

0.81

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over