Variant chr1-53909897-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000792.7(DIO1):c.682-34C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 1,607,938 control chromosomes in the GnomAD database, including 220,048 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as drug response (no stars).

Frequency

Genomes: 𝑓 0.45 ( 16505 hom., cov: 32)

Exomes 𝑓: 0.52 ( 203543 hom. )

Consequence

DIO1
NM_000792.7 intron

Scores

Clinical Significance

drug response no assertion criteria provided O:1

Conservation

PhyloP100: 0.0130

Variant links:

Genes affected

DIO1 (HGNC:2883): (iodothyronine deiodinase 1) The protein encoded by this gene belongs to the iodothyronine deiodinase family. It catalyzes the activation, as well as the inactivation of thyroid hormone by outer and inner ring deiodination, respectively. The activation reaction involves the conversion of the prohormone thyroxine (3,5,3',5'-tetraiodothyronine, T4), secreted by the thyroid gland, to the bioactive thyroid hormone (3,5,3'-triiodothyronine, T3) by 5'-deiodination. This protein provides most of the circulating T3, which is essential for growth, differentiation and basal metabolism in vertebrates. This protein is a selenoprotein, containing the rare amino acid selenocysteine (Sec) at its active site. Sec is encoded by the UGA codon, which normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, designated the Sec insertion sequence (SECIS) element, that is necessary for the recognition of UGA as a Sec codon, rather than as a stop signal. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jun 2018]

DIO1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIO1	NM_000792.7 link	c.682-34C>A		intron_variant	Intron 3 of 3	ENST00000361921.8	NP_000783.2	P49895-1A8K415

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIO1	ENST00000361921.8 link	c.682-34C>A		intron_variant	Intron 3 of 3	1	NM_000792.7	ENSP00000354643.4		P49895-1

Frequencies

GnomAD3 genomes

AF:

0.446

AC:

67674

AN:

151844

Hom.:

16490

Cov.:

show subpopulations

Gnomad AFR

AF:

0.235

Gnomad AMI

AF:

0.257

Gnomad AMR

AF:

0.585

Gnomad ASJ

AF:

0.407

Gnomad EAS

AF:

0.472

Gnomad SAS

AF:

0.624

Gnomad FIN

AF:

0.551

Gnomad MID

AF:

0.380

Gnomad NFE

AF:

0.517

Gnomad OTH

AF:

0.429

GnomAD3 exomes

AF:

0.531

AC:

132485

AN:

249382

Hom.:

37035

AF XY:

0.533

AC XY:

71933

AN XY:

134954

show subpopulations

Gnomad AFR exome

AF:

0.233

Gnomad AMR exome

AF:

0.710

Gnomad ASJ exome

AF:

0.400

Gnomad EAS exome

AF:

0.488

Gnomad SAS exome

AF:

0.636

Gnomad FIN exome

AF:

0.540

Gnomad NFE exome

AF:

0.508

Gnomad OTH exome

AF:

0.522

GnomAD4 exome

AF:

0.523

AC:

761769

AN:

1455976

Hom.:

203543

Cov.:

AF XY:

0.526

AC XY:

381038

AN XY:

724736

show subpopulations

Gnomad4 AFR exome

AF:

0.216

Gnomad4 AMR exome

AF:

0.691

Gnomad4 ASJ exome

AF:

0.398

Gnomad4 EAS exome

AF:

0.440

Gnomad4 SAS exome

AF:

0.629

Gnomad4 FIN exome

AF:

0.541

Gnomad4 NFE exome

AF:

0.525

Gnomad4 OTH exome

AF:

0.493

GnomAD4 genome

AF:

0.446

AC:

67713

AN:

151962

Hom.:

16505

Cov.:

AF XY:

0.452

AC XY:

33550

AN XY:

74256

show subpopulations

Gnomad4 AFR

AF:

0.235

Gnomad4 AMR

AF:

0.586

Gnomad4 ASJ

AF:

0.407

Gnomad4 EAS

AF:

0.471

Gnomad4 SAS

AF:

0.625

Gnomad4 FIN

AF:

0.551

Gnomad4 NFE

AF:

0.517

Gnomad4 OTH

AF:

0.433

Alfa

AF:

0.496

Hom.:

28608

Bravo

AF:

0.435

Asia WGS

AF:

0.535

AC:

1860

AN:

3478

ClinVar

Significance: drug response

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Levothyroxine response

Other:1

Pharmacogenomics/Precision medicine lab, University of Petra

Significance: drug response

Review Status: no assertion criteria provided

Collection Method: research

- the CC allele had the highest mean free T3 levels after levothyroxine replacement with decreasing concentrations for the CT then the TT genotypes. The CC was predictive of T3 dosage requirements

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.1

DANN

Benign

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over