dbSNP rs760297837: DUOX1:c.3524+15_3524+16delAT (chr15-45153493-AAT-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_175940.3(DUOX1):c.3524+15_3524+16delAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 1,191,280 control chromosomes in the GnomAD database, including 140,156 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.47 ( 15097 hom., cov: 0)

Exomes 𝑓: 0.39 ( 125059 hom. )

Consequence

DUOX1
NM_175940.3 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.571

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:

ENSG00000259539 (HGNC:):

ENSG00000259539 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 15-45153493-AAT-A is Benign according to our data. Variant chr15-45153493-AAT-A is described in ClinVar as [Benign]. Clinvar id is 402808.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DUOX1	NM_175940.3 link	c.3524+15_3524+16delAT		intron_variant	Intron 26 of 33	ENST00000389037.7	NP_787954.1	Q9NRD9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DUOX1	ENST00000389037.7 link	c.3524+15_3524+16delAT		intron_variant	Intron 26 of 33	1	NM_175940.3	ENSP00000373689.3		Q9NRD9-1

Frequencies

GnomAD3 genomes

AF:

0.465

AC:

61734

AN:

132640

Hom.:

15096

Cov.:

show subpopulations

Gnomad AFR

AF:

0.309

Gnomad AMI

AF:

0.773

Gnomad AMR

AF:

0.390

Gnomad ASJ

AF:

0.442

Gnomad EAS

AF:

0.0729

Gnomad SAS

AF:

0.346

Gnomad FIN

AF:

0.550

Gnomad MID

AF:

0.362

Gnomad NFE

AF:

0.570

Gnomad OTH

AF:

0.452

GnomAD3 exomes

AF:

0.349

AC:

82234

AN:

235906

Hom.:

22651

AF XY:

0.360

AC XY:

46031

AN XY:

127814

show subpopulations

Gnomad AFR exome

AF:

0.180

Gnomad AMR exome

AF:

0.218

Gnomad ASJ exome

AF:

0.361

Gnomad EAS exome

AF:

0.0485

Gnomad SAS exome

AF:

0.274

Gnomad FIN exome

AF:

0.407

Gnomad NFE exome

AF:

0.471

Gnomad OTH exome

AF:

0.400

GnomAD4 exome

AF:

0.386

AC:

408868

AN:

1058554

Hom.:

125059

AF XY:

0.392

AC XY:

213017

AN XY:

543496

show subpopulations

Gnomad4 AFR exome

AF:

0.171

Gnomad4 AMR exome

AF:

0.244

Gnomad4 ASJ exome

AF:

0.388

Gnomad4 EAS exome

AF:

0.0447

Gnomad4 SAS exome

AF:

0.304

Gnomad4 FIN exome

AF:

0.484

Gnomad4 NFE exome

AF:

0.423

Gnomad4 OTH exome

AF:

0.382

GnomAD4 genome

AF:

0.465

AC:

61727

AN:

132726

Hom.:

15097

Cov.:

AF XY:

0.459

AC XY:

29485

AN XY:

64242

show subpopulations

Gnomad4 AFR

AF:

0.309

Gnomad4 AMR

AF:

0.389

Gnomad4 ASJ

AF:

0.442

Gnomad4 EAS

AF:

0.0726

Gnomad4 SAS

AF:

0.345

Gnomad4 FIN

AF:

0.550

Gnomad4 NFE

AF:

0.570

Gnomad4 OTH

AF:

0.447

Alfa

AF:

0.224

Hom.:

1608

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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