rs8041911

Variant names:

• chr15-45150814-T-C
• rs8041911
• NM_175940.3:c.2888+113T>C

Variant summary

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

The NM_175940.3(DUOX1):​c.2888+113T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 1,023,650 control chromosomes in the GnomAD database, including 24,975 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 0.20 (3379 hom., cov: 32)
  • Exomes 𝑓: 0.21 (21596 hom.)
• Consequence: DUOX1 NM_175940.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.758
• Publications: 7 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]

LOC124903480 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175940.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUOX1	NM_175940.3	MANE Select	c.2888+113T>C		intron	N/A	NP_787954.1
	DUOX1	NM_017434.5		c.2888+113T>C		intron	N/A	NP_059130.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DUOX1	ENST00000389037.7	TSL:1 MANE Select	c.2888+113T>C		intron	N/A	ENSP00000373689.3
	DUOX1	ENST00000321429.8	TSL:1	c.2888+113T>C		intron	N/A	ENSP00000317997.4
	DUOX1	ENST00000557893.5	TSL:1	n.289+113T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30969 AN: 151912 Hom.: 3381 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.0575

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.233

GnomAD4 exome AF: 0.214 AC: 186652 AN: 871620 Hom.: 21596 AF XY: 0.220 AC XY: 98058 AN XY: 445632

African (AFR) AF: 0.183 AC: 3861 AN: 21104

American (AMR) AF: 0.150 AC: 4871 AN: 32448

Ashkenazi Jewish (ASJ) AF: 0.314 AC: 6244 AN: 19870

East Asian (EAS) AF: 0.0684 AC: 2318 AN: 33870

South Asian (SAS) AF: 0.323 AC: 21036 AN: 65166

European-Finnish (FIN) AF: 0.216 AC: 9027 AN: 41830

Middle Eastern (MID) AF: 0.333 AC: 1532 AN: 4596

European-Non Finnish (NFE) AF: 0.210 AC: 128771 AN: 612366

Other (OTH) AF: 0.223 AC: 8992 AN: 40370

GnomAD4 genome AF: 0.204 AC: 30970 AN: 152030 Hom.: 3379 Cov.: 32 AF XY: 0.205 AC XY: 15239 AN XY: 74308

African (AFR) AF: 0.184 AC: 7637 AN: 41452

American (AMR) AF: 0.199 AC: 3035 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 1103 AN: 3468

East Asian (EAS) AF: 0.0575 AC: 297 AN: 5168

South Asian (SAS) AF: 0.330 AC: 1585 AN: 4802

European-Finnish (FIN) AF: 0.206 AC: 2172 AN: 10568

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.213 AC: 14464 AN: 67972

Other (OTH) AF: 0.231 AC: 487 AN: 2112

Alfa AF: 0.218 Hom.: 5829

Bravo AF: 0.197

Asia WGS AF: 0.179 AC: 623 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.0
DANN	Benign	0.83
PhyloP100		-0.76
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs8041911; hg19: chr15-45443012; COSMIC: COSV58485589; COSMIC: COSV58485589;