chr15-45133666-G-A

Position:

• chr15-45133666-G-A

Variant summary

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

The NM_175940.3(DUOX1):​c.59-198G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 152,024 control chromosomes in the GnomAD database, including 16,430 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 0.42 (16430 hom., cov: 32)
• Consequence: DUOX1 NM_175940.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.421

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DUOX1	NM_175940.3	c.59-198G>A		intron_variant		ENST00000389037.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DUOX1	ENST00000389037.7	c.59-198G>A		intron_variant		1	NM_175940.3	P1
DUOX1	ENST00000321429.8	c.59-198G>A		intron_variant		1		P1
DUOX1	ENST00000558322.5	c.59-198G>A		intron_variant		2
DUOX1	ENST00000561220.6	c.59-198G>A		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.422 AC: 64162 AN: 151908 Hom.: 16436 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.666

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.437

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.422 AC: 64154 AN: 152024 Hom.: 16430 Cov.: 32 AF XY: 0.422 AC XY: 31331 AN XY: 74308

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.452

Gnomad4 ASJ AF: 0.476

Gnomad4 EAS AF: 0.319

Gnomad4 SAS AF: 0.416

Gnomad4 FIN AF: 0.577

Gnomad4 NFE AF: 0.575

Gnomad4 OTH AF: 0.433

Alfa AF: 0.537 Hom.: 34340

Bravo AF: 0.402

Asia WGS AF: 0.359 AC: 1249 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.3
DANN	Benign	0.66

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: rs1648282; hg19: chr15-45425864;