chr15-45164929-C-T

Variant names:

• chr15-45164929-C-T
• rs7169193
• NM_175940.3:c.*28C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_175940.3(DUOX1):​c.*28C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 1,607,690 control chromosomes in the GnomAD database, including 208,507 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 (27273 hom., cov: 32)
  • Exomes 𝑓: 0.48 (181234 hom.)
• Consequence: DUOX1 NM_175940.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.633
• Publications: 13 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• 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 rank	MANE	Protein	UniProt
DUOX1	NM_175940.3	c.*28C>T		3_prime_UTR_variant	Exon 34 of 34	ENST00000389037.7	NP_787954.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DUOX1	ENST00000389037.7	c.*28C>T		3_prime_UTR_variant	Exon 34 of 34	1	NM_175940.3	ENSP00000373689.3

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87710 AN: 151898 Hom.: 27212 Cov.: 32

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: 0.576

GnomAD2 exomes AF: 0.575 AC: 144028 AN: 250626 AF XY: 0.563

Gnomad AFR exome AF: 0.768

Gnomad AMR exome AF: 0.748

Gnomad ASJ exome AF: 0.550

Gnomad EAS exome AF: 0.944

Gnomad FIN exome AF: 0.482

Gnomad NFE exome AF: 0.445

Gnomad OTH exome AF: 0.527

GnomAD4 exome AF: 0.484 AC: 704173 AN: 1455676 Hom.: 181234 Cov.: 33 AF XY: 0.486 AC XY: 352044 AN XY: 724470

African (AFR) AF: 0.770 AC: 25749 AN: 33438

American (AMR) AF: 0.735 AC: 32850 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.553 AC: 14413 AN: 26054

East Asian (EAS) AF: 0.951 AC: 37732 AN: 39674

South Asian (SAS) AF: 0.614 AC: 52863 AN: 86134

European-Finnish (FIN) AF: 0.482 AC: 25735 AN: 53394

Middle Eastern (MID) AF: 0.593 AC: 3414 AN: 5760

European-Non Finnish (NFE) AF: 0.434 AC: 479914 AN: 1106364

Other (OTH) AF: 0.524 AC: 31503 AN: 60176

GnomAD4 genome AF: 0.578 AC: 87830 AN: 152014 Hom.: 27273 Cov.: 32 AF XY: 0.584 AC XY: 43361 AN XY: 74304

African (AFR) AF: 0.759 AC: 31443 AN: 41454

American (AMR) AF: 0.643 AC: 9830 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.563 AC: 1955 AN: 3470

East Asian (EAS) AF: 0.942 AC: 4862 AN: 5160

South Asian (SAS) AF: 0.635 AC: 3066 AN: 4828

European-Finnish (FIN) AF: 0.479 AC: 5046 AN: 10540

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.441 AC: 30005 AN: 67964

Other (OTH) AF: 0.580 AC: 1227 AN: 2114

Alfa AF: 0.516 Hom.: 33162

Bravo AF: 0.598

Asia WGS AF: 0.751 AC: 2609 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.9
DANN	Benign	0.89
PhyloP100		0.63
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: rs7169193; hg19: chr15-45457127; COSMIC: COSV107333901; COSMIC: COSV107333901;