Variant rs1706804 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_175940.3(DUOX1):c.3228A>G(p.Thr1076=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 1,613,700 control chromosomes in the GnomAD database, including 352,550 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 0.60 ( 28438 hom., cov: 32)

Exomes 𝑓: 0.66 ( 324112 hom. )

Consequence

DUOX1
NM_175940.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.53

Variant links:

Genes affected

DUOX1 (HGNC:3062): (dual oxidase 1) The protein encoded by this gene is a glycoprotein and a member of the NADPH oxidase family. The synthesis of thyroid hormone is catalyzed by a protein complex located at the apical membrane of thyroid follicular cells. This complex contains an iodide transporter, thyroperoxidase, and a peroxide generating system that includes proteins encoded by this gene and the similar DUOX2 gene. This protein is known as dual oxidase because it has both a peroxidase homology domain and a gp91phox domain. This protein generates hydrogen peroxide and thereby plays a role in the activity of thyroid peroxidase, lactoperoxidase, and in lactoperoxidase-mediated antimicrobial defense at mucosal surfaces. Two alternatively spliced transcript variants encoding the same protein have been described for this gene. [provided by RefSeq, Jul 2012]

DUOX1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP7

Synonymous conserved (PhyloP=-2.53 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DUOX1	NM_175940.3 linkuse as main transcript	c.3228A>G	p.Thr1076=	synonymous_variant	25/34	ENST00000389037.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DUOX1	ENST00000389037.7 linkuse as main transcript	c.3228A>G	p.Thr1076=	synonymous_variant	25/34	1	NM_175940.3	P1	Q9NRD9-1

Frequencies

GnomAD3 genomes

AF:

0.604

AC:

91742

AN:

151964

Hom.:

28436

Cov.:

show subpopulations

Gnomad AFR

AF:

0.476

Gnomad AMI

AF:

0.802

Gnomad AMR

AF:

0.589

Gnomad ASJ

AF:

0.588

Gnomad EAS

AF:

0.477

Gnomad SAS

AF:

0.719

Gnomad FIN

AF:

0.661

Gnomad MID

AF:

0.611

Gnomad NFE

AF:

0.675

Gnomad OTH

AF:

0.611

GnomAD3 exomes

AF:

0.625

AC:

156807

AN:

250926

Hom.:

50118

AF XY:

0.637

AC XY:

86456

AN XY:

135668

show subpopulations

Gnomad AFR exome

AF:

0.470

Gnomad AMR exome

AF:

0.509

Gnomad ASJ exome

AF:

0.594

Gnomad EAS exome

AF:

0.482

Gnomad SAS exome

AF:

0.711

Gnomad FIN exome

AF:

0.659

Gnomad NFE exome

AF:

0.677

Gnomad OTH exome

AF:

0.646

GnomAD4 exome

AF:

0.663

AC:

969356

AN:

1461618

Hom.:

324112

Cov.:

AF XY:

0.665

AC XY:

483576

AN XY:

727124

show subpopulations

Gnomad4 AFR exome

AF:

0.469

Gnomad4 AMR exome

AF:

0.515

Gnomad4 ASJ exome

AF:

0.591

Gnomad4 EAS exome

AF:

0.496

Gnomad4 SAS exome

AF:

0.707

Gnomad4 FIN exome

AF:

0.658

Gnomad4 NFE exome

AF:

0.681

Gnomad4 OTH exome

AF:

0.642

GnomAD4 genome

AF:

0.603

AC:

91769

AN:

152082

Hom.:

28438

Cov.:

AF XY:

0.606

AC XY:

45054

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.476

Gnomad4 AMR

AF:

0.589

Gnomad4 ASJ

AF:

0.588

Gnomad4 EAS

AF:

0.477

Gnomad4 SAS

AF:

0.718

Gnomad4 FIN

AF:

0.661

Gnomad4 NFE

AF:

0.675

Gnomad4 OTH

AF:

0.609

Alfa

AF:

0.648

Hom.:

34654

Bravo

AF:

0.588

Asia WGS

AF:

0.616

AC:

2148

AN:

3478

EpiCase

AF:

0.672

EpiControl

AF:

0.671

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.59

DANN

Benign

0.67

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