rs1366813

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000379.4(XDH):c.3276+12A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.768 in 1,613,232 control chromosomes in the GnomAD database, including 476,581 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.76 ( 43796 hom., cov: 33)

Exomes 𝑓: 0.77 ( 432785 hom. )

Consequence

XDH
NM_000379.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -2.11

Publications

10 publications found

Variant links:

Genes affected

XDH (HGNC:12805): (xanthine dehydrogenase) Xanthine dehydrogenase belongs to the group of molybdenum-containing hydroxylases involved in the oxidative metabolism of purines. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. Xanthine dehydrogenase can be converted to xanthine oxidase by reversible sulfhydryl oxidation or by irreversible proteolytic modification. Defects in xanthine dehydrogenase cause xanthinuria, may contribute to adult respiratory stress syndrome, and may potentiate influenza infection through an oxygen metabolite-dependent mechanism. [provided by RefSeq, Jan 2014]

XDH Gene-Disease associations (from GenCC):

xanthinuria type I
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

XDH links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 2-31347510-T-C is Benign according to our data. Variant chr2-31347510-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 191300.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
XDH	NM_000379.4 link	c.3276+12A>G	intron_variant	Intron 29 of 35	ENST00000379416.4	NP_000370.2	P47989
XDH	XM_011533095.3 link	c.3273+12A>G	intron_variant	Intron 29 of 35		XP_011531397.1
XDH	XM_011533096.3 link	c.*559A>G	downstream_gene_variant			XP_011531398.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XDH	ENST00000379416.4 link	c.3276+12A>G		intron_variant	Intron 29 of 35	1	NM_000379.4	ENSP00000368727.3		P47989

Frequencies

GnomAD3 genomes

AF:

0.758

AC:

115224

AN:

152080

Hom.:

43768

Cov.:

show subpopulations

Gnomad AFR

AF:

0.726

Gnomad AMI

AF:

0.898

Gnomad AMR

AF:

0.735

Gnomad ASJ

AF:

0.814

Gnomad EAS

AF:

0.847

Gnomad SAS

AF:

0.830

Gnomad FIN

AF:

0.764

Gnomad MID

AF:

0.722

Gnomad NFE

AF:

0.765

Gnomad OTH

AF:

0.760

GnomAD2 exomes

AF:

0.776

AC:

194993

AN:

251154

AF XY:

0.780

show subpopulations

Gnomad AFR exome

AF:

0.724

Gnomad AMR exome

AF:

0.742

Gnomad ASJ exome

AF:

0.816

Gnomad EAS exome

AF:

0.851

Gnomad FIN exome

AF:

0.757

Gnomad NFE exome

AF:

0.768

Gnomad OTH exome

AF:

0.766

GnomAD4 exome

AF:

0.769

AC:

1123791

AN:

1461034

Hom.:

432785

Cov.:

AF XY:

0.772

AC XY:

560782

AN XY:

726858

show subpopulations

African (AFR)

AF:

0.714

AC:

23893

AN:

33456

American (AMR)

AF:

0.742

AC:

33168

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.822

AC:

21488

AN:

26132

East Asian (EAS)

AF:

0.857

AC:

34015

AN:

39698

South Asian (SAS)

AF:

0.837

AC:

72152

AN:

86206

European-Finnish (FIN)

AF:

0.750

AC:

40052

AN:

53400

Middle Eastern (MID)

AF:

0.785

AC:

4108

AN:

5236

European-Non Finnish (NFE)

AF:

0.763

AC:

848398

AN:

1111886

Other (OTH)

AF:

0.771

AC:

46517

AN:

60306

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

15158

30317

45475

60634

75792

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20472

40944

61416

81888

102360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.758

AC:

115304

AN:

152198

Hom.:

43796

Cov.:

AF XY:

0.758

AC XY:

56436

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.726

AC:

30145

AN:

41516

American (AMR)

AF:

0.734

AC:

11238

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.814

AC:

2826

AN:

3470

East Asian (EAS)

AF:

0.846

AC:

4361

AN:

5152

South Asian (SAS)

AF:

0.829

AC:

4001

AN:

4826

European-Finnish (FIN)

AF:

0.764

AC:

8102

AN:

10606

Middle Eastern (MID)

AF:

0.724

AC:

213

AN:

294

European-Non Finnish (NFE)

AF:

0.765

AC:

51999

AN:

68010

Other (OTH)

AF:

0.758

AC:

1600

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1455

2909

4364

5818

7273

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

864

1728

2592

3456

4320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.766

Hom.:

67504

Bravo

AF:

0.756

Asia WGS

AF:

0.792

AC:

2754

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hereditary xanthinuria type 1

Benign:5

Sep 27, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jan 31, 2017

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 28, 2016

Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:research

- -

not provided

Benign:2

Nov 13, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Xanthinuria type II

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.14

(source)

DANN

Benign

0.37

PhyloP100

-2.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over