rs207440

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_000379.4(XDH):c.3717G>A(p.Glu1239Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0575 in 1,614,126 control chromosomes in the GnomAD database, including 2,861 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.052 ( 230 hom., cov: 32)

Exomes 𝑓: 0.058 ( 2631 hom. )

Consequence

XDH
NM_000379.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.552

Publications

12 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 2-31339546-C-T is Benign according to our data. Variant chr2-31339546-C-T is described in ClinVar as Benign. ClinVar VariationId is 255970.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.552 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XDH	NM_000379.4 link	c.3717G>A	p.Glu1239Glu	synonymous_variant	Exon 34 of 36	ENST00000379416.4	NP_000370.2
XDH	XM_011533095.3 link	c.3714G>A	p.Glu1238Glu	synonymous_variant	Exon 34 of 36		XP_011531397.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XDH	ENST00000379416.4 link	c.3717G>A	p.Glu1239Glu	synonymous_variant	Exon 34 of 36	1	NM_000379.4	ENSP00000368727.3

Frequencies

GnomAD3 genomes

AF:

0.0523

AC:

7958

AN:

152130

Hom.:

230

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0569

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0318

Gnomad ASJ

AF:

0.0438

Gnomad EAS

AF:

0.00541

Gnomad SAS

AF:

0.0694

Gnomad FIN

AF:

0.0425

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0591

Gnomad OTH

AF:

0.0483

GnomAD2 exomes

AF:

0.0491

AC:

12346

AN:

251484

AF XY:

0.0519

show subpopulations

Gnomad AFR exome

AF:

0.0567

Gnomad AMR exome

AF:

0.0218

Gnomad ASJ exome

AF:

0.0425

Gnomad EAS exome

AF:

0.00375

Gnomad FIN exome

AF:

0.0381

Gnomad NFE exome

AF:

0.0596

Gnomad OTH exome

AF:

0.0525

GnomAD4 exome

AF:

0.0580

AC:

84827

AN:

1461878

Hom.:

2631

Cov.:

AF XY:

0.0587

AC XY:

42661

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.0593

AC:

1987

AN:

33480

American (AMR)

AF:

0.0232

AC:

1037

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0434

AC:

1134

AN:

26136

East Asian (EAS)

AF:

0.00685

AC:

272

AN:

39700

South Asian (SAS)

AF:

0.0732

AC:

6317

AN:

86258

European-Finnish (FIN)

AF:

0.0387

AC:

2065

AN:

53418

Middle Eastern (MID)

AF:

0.0565

AC:

326

AN:

5766

European-Non Finnish (NFE)

AF:

0.0614

AC:

68260

AN:

1112000

Other (OTH)

AF:

0.0568

AC:

3429

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

5563

11126

16689

22252

27815

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2556

5112

7668

10224

12780

<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:

0.0523

AC:

7965

AN:

152248

Hom.:

230

Cov.:

AF XY:

0.0507

AC XY:

3777

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.0569

AC:

2365

AN:

41552

American (AMR)

AF:

0.0318

AC:

486

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0438

AC:

152

AN:

3472

East Asian (EAS)

AF:

0.00542

AC:

AN:

5168

South Asian (SAS)

AF:

0.0692

AC:

334

AN:

4824

European-Finnish (FIN)

AF:

0.0425

AC:

451

AN:

10614

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0591

AC:

4021

AN:

68008

Other (OTH)

AF:

0.0483

AC:

102

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

392

784

1176

1568

1960

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

184

276

368

460

<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:

0.0567

Hom.:

1082

Bravo

AF:

0.0510

Asia WGS

AF:

0.0560

AC:

194

AN:

3478

EpiCase

AF:

0.0595

EpiControl

AF:

0.0607

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Mar 07, 2020

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

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 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.

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

-0.35

CADD

Benign

6.6

(source)

DANN

Benign

0.56

PhyloP100

0.55

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