2-31348920-A-G

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.3030T>C(p.Phe1010Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.773 in 1,612,262 control chromosomes in the GnomAD database, including 482,176 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.78 ( 46008 hom., cov: 34)

Exomes 𝑓: 0.77 ( 436168 hom. )

Consequence

XDH
NM_000379.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.46

Publications

37 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=-0.48).

BP6

Variant 2-31348920-A-G is Benign according to our data. Variant chr2-31348920-A-G is described in ClinVar as Benign. ClinVar VariationId is 255968.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.46 with no splicing effect.

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
XDH	NM_000379.4 link	c.3030T>C	p.Phe1010Phe	synonymous_variant	Exon 27 of 36	ENST00000379416.4	NP_000370.2
XDH	XM_011533095.3 link	c.3027T>C	p.Phe1009Phe	synonymous_variant	Exon 27 of 36		XP_011531397.1
XDH	XM_011533096.3 link	c.3030T>C	p.Phe1010Phe	synonymous_variant	Exon 27 of 29		XP_011531398.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XDH	ENST00000379416.4 link	c.3030T>C	p.Phe1010Phe	synonymous_variant	Exon 27 of 36	1	NM_000379.4	ENSP00000368727.3

Frequencies

GnomAD3 genomes

AF:

0.777

AC:

118197

AN:

152148

Hom.:

45976

Cov.:

show subpopulations

Gnomad AFR

AF:

0.790

Gnomad AMI

AF:

0.898

Gnomad AMR

AF:

0.742

Gnomad ASJ

AF:

0.818

Gnomad EAS

AF:

0.847

Gnomad SAS

AF:

0.838

Gnomad FIN

AF:

0.768

Gnomad MID

AF:

0.728

Gnomad NFE

AF:

0.765

Gnomad OTH

AF:

0.769

GnomAD2 exomes

AF:

0.783

AC:

196774

AN:

251254

AF XY:

0.786

show subpopulations

Gnomad AFR exome

AF:

0.792

Gnomad AMR exome

AF:

0.745

Gnomad ASJ exome

AF:

0.822

Gnomad EAS exome

AF:

0.851

Gnomad FIN exome

AF:

0.759

Gnomad NFE exome

AF:

0.769

Gnomad OTH exome

AF:

0.770

GnomAD4 exome

AF:

0.772

AC:

1127631

AN:

1459996

Hom.:

436168

Cov.:

AF XY:

0.775

AC XY:

562718

AN XY:

726450

show subpopulations

African (AFR)

AF:

0.787

AC:

26309

AN:

33450

American (AMR)

AF:

0.745

AC:

33295

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.828

AC:

21619

AN:

26120

East Asian (EAS)

AF:

0.858

AC:

34035

AN:

39688

South Asian (SAS)

AF:

0.846

AC:

72912

AN:

86214

European-Finnish (FIN)

AF:

0.752

AC:

40158

AN:

53404

Middle Eastern (MID)

AF:

0.793

AC:

4565

AN:

5760

European-Non Finnish (NFE)

AF:

0.764

AC:

847842

AN:

1110308

Other (OTH)

AF:

0.777

AC:

46896

AN:

60342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

13033

26066

39099

52132

65165

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20444

40888

61332

81776

102220

<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:

0.777

AC:

118281

AN:

152266

Hom.:

46008

Cov.:

AF XY:

0.777

AC XY:

57849

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.790

AC:

32841

AN:

41550

American (AMR)

AF:

0.741

AC:

11347

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.818

AC:

2840

AN:

3472

East Asian (EAS)

AF:

0.846

AC:

4386

AN:

5182

South Asian (SAS)

AF:

0.837

AC:

4043

AN:

4830

European-Finnish (FIN)

AF:

0.768

AC:

8140

AN:

10600

Middle Eastern (MID)

AF:

0.731

AC:

215

AN:

294

European-Non Finnish (NFE)

AF:

0.765

AC:

52027

AN:

68006

Other (OTH)

AF:

0.767

AC:

1623

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1394

2787

4181

5574

6968

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

870

1740

2610

3480

4350

<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:

0.773

Hom.:

216184

Bravo

AF:

0.778

Asia WGS

AF:

0.796

AC:

2767

AN:

3478

EpiCase

AF:

0.771

EpiControl

AF:

0.776

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

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

-0.48

CADD

Benign

8.6

(source)

DANN

Benign

0.71

PhyloP100

1.5

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