rs2295475

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000379.4(XDH):c.2211C>T(p.Ile737Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 1,614,036 control chromosomes in the GnomAD database, including 74,844 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5554 hom., cov: 34)

Exomes 𝑓: 0.30 ( 69290 hom. )

Consequence

XDH
NM_000379.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.294

Publications

30 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 2-31366981-G-A is Benign according to our data. Variant chr2-31366981-G-A is described in ClinVar as Benign. ClinVar VariationId is 255967.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.294 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XDH	NM_000379.4 link	c.2211C>T	p.Ile737Ile	synonymous_variant	Exon 21 of 36	ENST00000379416.4	NP_000370.2	P47989
XDH	XM_011533095.3 link	c.2208C>T	p.Ile736Ile	synonymous_variant	Exon 21 of 36		XP_011531397.1
XDH	XM_011533096.3 link	c.2211C>T	p.Ile737Ile	synonymous_variant	Exon 21 of 29		XP_011531398.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XDH	ENST00000379416.4 link	c.2211C>T	p.Ile737Ile	synonymous_variant	Exon 21 of 36	1	NM_000379.4	ENSP00000368727.3		P47989

Frequencies

GnomAD3 genomes

AF:

0.250

AC:

38007

AN:

152120

Hom.:

5554

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0881

Gnomad AMI

AF:

0.334

Gnomad AMR

AF:

0.320

Gnomad ASJ

AF:

0.236

Gnomad EAS

AF:

0.345

Gnomad SAS

AF:

0.355

Gnomad FIN

AF:

0.321

Gnomad MID

AF:

0.223

Gnomad NFE

AF:

0.307

Gnomad OTH

AF:

0.249

GnomAD2 exomes

AF:

0.309

AC:

77569

AN:

251432

AF XY:

0.310

show subpopulations

Gnomad AFR exome

AF:

0.0823

Gnomad AMR exome

AF:

0.396

Gnomad ASJ exome

AF:

0.244

Gnomad EAS exome

AF:

0.342

Gnomad FIN exome

AF:

0.309

Gnomad NFE exome

AF:

0.304

Gnomad OTH exome

AF:

0.286

GnomAD4 exome

AF:

0.304

AC:

444675

AN:

1461796

Hom.:

69290

Cov.:

AF XY:

0.306

AC XY:

222484

AN XY:

727184

show subpopulations

African (AFR)

AF:

0.0755

AC:

2526

AN:

33478

American (AMR)

AF:

0.388

AC:

17363

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.243

AC:

6340

AN:

26134

East Asian (EAS)

AF:

0.352

AC:

13990

AN:

39700

South Asian (SAS)

AF:

0.347

AC:

29963

AN:

86256

European-Finnish (FIN)

AF:

0.304

AC:

16255

AN:

53414

Middle Eastern (MID)

AF:

0.232

AC:

1340

AN:

5768

European-Non Finnish (NFE)

AF:

0.306

AC:

339848

AN:

1111938

Other (OTH)

AF:

0.282

AC:

17050

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

21093

42185

63278

84370

105463

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11220

22440

33660

44880

56100

<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:

0.250

AC:

38002

AN:

152240

Hom.:

5554

Cov.:

AF XY:

0.254

AC XY:

18933

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.0878

AC:

3649

AN:

41572

American (AMR)

AF:

0.320

AC:

4889

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.236

AC:

819

AN:

3472

East Asian (EAS)

AF:

0.345

AC:

1782

AN:

5168

South Asian (SAS)

AF:

0.354

AC:

1706

AN:

4822

European-Finnish (FIN)

AF:

0.321

AC:

3400

AN:

10586

Middle Eastern (MID)

AF:

0.218

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.307

AC:

20859

AN:

68010

Other (OTH)

AF:

0.250

AC:

529

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1476

2951

4427

5902

7378

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

402

804

1206

1608

2010

<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:

0.287

Hom.:

29844

Bravo

AF:

0.242

Asia WGS

AF:

0.360

AC:

1251

AN:

3478

EpiCase

AF:

0.297

EpiControl

AF:

0.297

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 13, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hereditary xanthinuria type 1

Benign:2

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 12, 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. -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Xanthinuria type II

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.68

CADD

Benign

0.015

(source)

DANN

Benign

0.63

PhyloP100

-0.29

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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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