15-45146339-C-T

Variant names:

• chr15-45146339-C-T
• rs1648305
• NM_175940.3:c.2323-1094C>T

Variant summary

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

The NM_175940.3(DUOX1):​c.2323-1094C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.638 in 152,034 control chromosomes in the GnomAD database, including 32,236 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 0.64 (32236 hom., cov: 32)
• Consequence: DUOX1 NM_175940.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0920

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DUOX1	NM_175940.3	c.2323-1094C>T		intron_variant	Intron 18 of 33	ENST00000389037.7	NP_787954.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DUOX1	ENST00000389037.7	c.2323-1094C>T		intron_variant	Intron 18 of 33	1	NM_175940.3	ENSP00000373689.3
DUOX1	ENST00000321429.8	c.2323-1094C>T		intron_variant	Intron 19 of 34	1		ENSP00000317997.4
DUOX1	ENST00000561166.1	c.1261-1094C>T		intron_variant	Intron 8 of 23	2		ENSP00000454065.1
DUOX1	ENST00000561220.6	n.*862-1094C>T		intron_variant	Intron 17 of 32	5		ENSP00000452623.1

Frequencies

GnomAD3 genomes AF: 0.639 AC: 97006 AN: 151914 Hom.: 32214 Cov.: 32

Gnomad AFR AF: 0.494

Gnomad AMI AF: 0.901

Gnomad AMR AF: 0.624

Gnomad ASJ AF: 0.633

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.475

Gnomad FIN AF: 0.763

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.739

Gnomad OTH AF: 0.638

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

GnomAD4 genome AF: 0.638 AC: 97072 AN: 152034 Hom.: 32236 Cov.: 32 AF XY: 0.635 AC XY: 47174 AN XY: 74290

Gnomad4 AFR AF: 0.494

Gnomad4 AMR AF: 0.624

Gnomad4 ASJ AF: 0.633

Gnomad4 EAS AF: 0.381

Gnomad4 SAS AF: 0.475

Gnomad4 FIN AF: 0.763

Gnomad4 NFE AF: 0.739

Gnomad4 OTH AF: 0.634

Alfa AF: 0.706 Hom.: 77339

Bravo AF: 0.627

Asia WGS AF: 0.462 AC: 1606 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.8
DANN	Benign	0.56

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: rs1648305; hg19: chr15-45438537;