rs760297837

Variant names:

• chr15-45153493-AAT-A
• rs760297837
• NM_175940.3:c.3524+15_3524+16delAT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.571
• Publications: 0 publications found

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]

ENSG00000259539 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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	c.3524+15_3524+16delAT		intron_variant	Intron 26 of 33	ENST00000389037.7	NP_787954.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.465 AC: 61734 AN: 132640 Hom.: 15096 Cov.: 0

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

GnomAD2 exomes AF: 0.349 AC: 82234 AN: 235906 AF XY: 0.360

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 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

African (AFR) AF: 0.171 AC: 4699 AN: 27444

American (AMR) AF: 0.244 AC: 10750 AN: 44064

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 9173 AN: 23612

East Asian (EAS) AF: 0.0447 AC: 1711 AN: 38302

South Asian (SAS) AF: 0.304 AC: 24374 AN: 80134

European-Finnish (FIN) AF: 0.484 AC: 25116 AN: 51938

Middle Eastern (MID) AF: 0.338 AC: 1692 AN: 5004

European-Non Finnish (NFE) AF: 0.423 AC: 313102 AN: 740258

Other (OTH) AF: 0.382 AC: 18251 AN: 47798

GnomAD4 genome AF: 0.465 AC: 61727 AN: 132726 Hom.: 15097 Cov.: 0 AF XY: 0.459 AC XY: 29485 AN XY: 64242

African (AFR) AF: 0.309 AC: 9403 AN: 30478

American (AMR) AF: 0.389 AC: 5206 AN: 13382

Ashkenazi Jewish (ASJ) AF: 0.442 AC: 1463 AN: 3310

East Asian (EAS) AF: 0.0726 AC: 279 AN: 3844

South Asian (SAS) AF: 0.345 AC: 1444 AN: 4186

European-Finnish (FIN) AF: 0.550 AC: 5141 AN: 9344

Middle Eastern (MID) AF: 0.378 AC: 102 AN: 270

European-Non Finnish (NFE) AF: 0.570 AC: 37156 AN: 65138

Other (OTH) AF: 0.447 AC: 837 AN: 1874

Alfa AF: 0.224 Hom.: 1608

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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
PhyloP100		0.57
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs760297837; hg19: chr15-45445691;