rs8041911

Positions:

• chr15-45150814-T-C

Variant summary

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

The ENST00000389037.7(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 ENST00000389037.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.758

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DUOX1	NM_175940.3	c.2888+113T>C		intron_variant		ENST00000389037.7	NP_787954.1
LOC124903480	XR_007064607.1	n.391+676A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DUOX1	ENST00000389037.7	c.2888+113T>C		intron_variant		1	NM_175940.3	ENSP00000373689	P1

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

Gnomad4 AFR exome AF: 0.183

Gnomad4 AMR exome AF: 0.150

Gnomad4 ASJ exome AF: 0.314

Gnomad4 EAS exome AF: 0.0684

Gnomad4 SAS exome AF: 0.323

Gnomad4 FIN exome AF: 0.216

Gnomad4 NFE exome AF: 0.210

Gnomad4 OTH exome AF: 0.223

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

Gnomad4 AFR AF: 0.184

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.318

Gnomad4 EAS AF: 0.0575

Gnomad4 SAS AF: 0.330

Gnomad4 FIN AF: 0.206

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.231

Alfa AF: 0.221 Hom.: 4235

Bravo AF: 0.197

Asia WGS AF: 0.179 AC: 623 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.0
DANN	Benign	0.83

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

Publications

LitVar

Other links and lift over

dbSNP: rs8041911; hg19: chr15-45443012; COSMIC: COSV58485589; COSMIC: COSV58485589;