dbSNP rs2294512: DIO1:c.338-33G>A (chr1-53904633-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_000792.7(DIO1):c.338-33G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 1,601,710 control chromosomes in the GnomAD database, including 82,266 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 0.35 ( 10158 hom., cov: 31)

Exomes 𝑓: 0.31 ( 72108 hom. )

Consequence

DIO1
NM_000792.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0610

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:

LOC124904180 (HGNC:):

LOC124904180 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=-0.95).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIO1	NM_000792.7 link	c.338-33G>A		intron_variant	Intron 1 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.338-33G>A		intron_variant	Intron 1 of 3	1	NM_000792.7	ENSP00000354643.4		P49895-1

Frequencies

GnomAD3 genomes

AF:

0.351

AC:

53209

AN:

151756

Hom.:

10135

Cov.:

show subpopulations

Gnomad AFR

AF:

0.485

Gnomad AMI

AF:

0.212

Gnomad AMR

AF:

0.263

Gnomad ASJ

AF:

0.234

Gnomad EAS

AF:

0.623

Gnomad SAS

AF:

0.357

Gnomad FIN

AF:

0.311

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.284

Gnomad OTH

AF:

0.297

GnomAD3 exomes

AF:

0.331

AC:

79792

AN:

241202

Hom.:

14593

AF XY:

0.325

AC XY:

42577

AN XY:

131030

show subpopulations

Gnomad AFR exome

AF:

0.495

Gnomad AMR exome

AF:

0.291

Gnomad ASJ exome

AF:

0.230

Gnomad EAS exome

AF:

0.633

Gnomad SAS exome

AF:

0.337

Gnomad FIN exome

AF:

0.305

Gnomad NFE exome

AF:

0.286

Gnomad OTH exome

AF:

0.287

GnomAD4 exome

AF:

0.307

AC:

444813

AN:

1449836

Hom.:

72108

Cov.:

AF XY:

0.306

AC XY:

220836

AN XY:

721186

show subpopulations

Gnomad4 AFR exome

AF:

0.499

Gnomad4 AMR exome

AF:

0.288

Gnomad4 ASJ exome

AF:

0.232

Gnomad4 EAS exome

AF:

0.629

Gnomad4 SAS exome

AF:

0.339

Gnomad4 FIN exome

AF:

0.306

Gnomad4 NFE exome

AF:

0.290

Gnomad4 OTH exome

AF:

0.310

GnomAD4 genome

AF:

0.351

AC:

53280

AN:

151874

Hom.:

10158

Cov.:

AF XY:

0.350

AC XY:

25978

AN XY:

74212

show subpopulations

Gnomad4 AFR

AF:

0.485

Gnomad4 AMR

AF:

0.263

Gnomad4 ASJ

AF:

0.234

Gnomad4 EAS

AF:

0.623

Gnomad4 SAS

AF:

0.356

Gnomad4 FIN

AF:

0.311

Gnomad4 NFE

AF:

0.284

Gnomad4 OTH

AF:

0.297

Alfa

AF:

0.300

Hom.:

5161

Bravo

AF:

0.356

Asia WGS

AF:

0.499

AC:

1735

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.70

DANN

Benign

0.24

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over