chr15-45152320-A-G

Variant names:

• chr15-45152320-A-G
• rs1706804
• NM_175940.3:c.3228A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_175940.3(DUOX1):​c.3228A>G​(p.Thr1076Thr) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.53
• Publications: 25 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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DUOX1	NM_175940.3	c.3228A>G	p.Thr1076Thr	synonymous_variant	Exon 25 of 34	ENST00000389037.7	NP_787954.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DUOX1	ENST00000389037.7	c.3228A>G	p.Thr1076Thr	synonymous_variant	Exon 25 of 34	1	NM_175940.3	ENSP00000373689.3

Frequencies

GnomAD3 genomes AF: 0.604 AC: 91742 AN: 151964 Hom.: 28436 Cov.: 32

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

GnomAD2 exomes AF: 0.625 AC: 156807 AN: 250926 AF XY: 0.637

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 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.: 66 AF XY: 0.665 AC XY: 483576 AN XY: 727124

African (AFR) AF: 0.469 AC: 15715 AN: 33480

American (AMR) AF: 0.515 AC: 23027 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.591 AC: 15457 AN: 26136

East Asian (EAS) AF: 0.496 AC: 19675 AN: 39688

South Asian (SAS) AF: 0.707 AC: 60964 AN: 86250

European-Finnish (FIN) AF: 0.658 AC: 35079 AN: 53350

Middle Eastern (MID) AF: 0.611 AC: 3523 AN: 5768

European-Non Finnish (NFE) AF: 0.681 AC: 757153 AN: 1111876

Other (OTH) AF: 0.642 AC: 38763 AN: 60384

GnomAD4 genome AF: 0.603 AC: 91769 AN: 152082 Hom.: 28438 Cov.: 32 AF XY: 0.606 AC XY: 45054 AN XY: 74342

African (AFR) AF: 0.476 AC: 19729 AN: 41464

American (AMR) AF: 0.589 AC: 9012 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.588 AC: 2041 AN: 3470

East Asian (EAS) AF: 0.477 AC: 2463 AN: 5164

South Asian (SAS) AF: 0.718 AC: 3461 AN: 4820

European-Finnish (FIN) AF: 0.661 AC: 7007 AN: 10598

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.675 AC: 45860 AN: 67952

Other (OTH) AF: 0.609 AC: 1287 AN: 2114

Alfa AF: 0.639 Hom.: 46940

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
PhyloP100		-2.5
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: rs1706804; hg19: chr15-45444518; COSMIC: COSV58478069; COSMIC: COSV58478069;