15-45165151-A-G

Position:

• chr15-45165151-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_175940.3(DUOX1):​c.*250A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 543,486 control chromosomes in the GnomAD database, including 85,772 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 0.58 (27309 hom., cov: 33)
  • Exomes 𝑓: 0.52 (58463 hom.)
• Consequence: DUOX1 NM_175940.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.309

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUOX1	NM_175940.3	c.*250A>G		3_prime_UTR_variant	34/34	ENST00000389037.7	NP_787954.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DUOX1	ENST00000389037.7	c.*250A>G		3_prime_UTR_variant	34/34	1	NM_175940.3	ENSP00000373689.3

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87783 AN: 152020 Hom.: 27248 Cov.: 33

Gnomad AFR AF: 0.758

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.643

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.942

Gnomad SAS AF: 0.633

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.577

GnomAD4 exome AF: 0.524 AC: 205259 AN: 391348 Hom.: 58463 Cov.: 3 AF XY: 0.525 AC XY: 107086 AN XY: 203834

Gnomad4 AFR exome AF: 0.759

Gnomad4 AMR exome AF: 0.680

Gnomad4 ASJ exome AF: 0.560

Gnomad4 EAS exome AF: 0.953

Gnomad4 SAS exome AF: 0.609

Gnomad4 FIN exome AF: 0.483

Gnomad4 NFE exome AF: 0.442

Gnomad4 OTH exome AF: 0.535

GnomAD4 genome AF: 0.578 AC: 87904 AN: 152138 Hom.: 27309 Cov.: 33 AF XY: 0.584 AC XY: 43399 AN XY: 74372

Gnomad4 AFR AF: 0.758

Gnomad4 AMR AF: 0.643

Gnomad4 ASJ AF: 0.563

Gnomad4 EAS AF: 0.942

Gnomad4 SAS AF: 0.635

Gnomad4 FIN AF: 0.479

Gnomad4 NFE AF: 0.442

Gnomad4 OTH AF: 0.582

Alfa AF: 0.490 Hom.: 14473

Bravo AF: 0.598

Asia WGS AF: 0.750 AC: 2607 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.2
DANN	Benign	0.52

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

Other links and lift over

dbSNP: rs1648312; hg19: chr15-45457349;