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GeneBe

2-31348920-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000379.4(XDH):c.3030T>C(p.Phe1010=) 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

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.46
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 255968.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-31348920-A-G is described in Lovd as [Benign].
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/exons MANE UniProt
XDHNM_000379.4 linkuse as main transcriptc.3030T>C p.Phe1010= synonymous_variant 27/36 ENST00000379416.4
XDHXM_011533095.3 linkuse as main transcriptc.3027T>C p.Phe1009= synonymous_variant 27/36
XDHXM_011533096.3 linkuse as main transcriptc.3030T>C p.Phe1010= synonymous_variant 27/29

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
XDHENST00000379416.4 linkuse as main transcriptc.3030T>C p.Phe1010= synonymous_variant 27/361 NM_000379.4 P1

Frequencies

GnomAD3 genomes
AF:
0.777
AC:
118197
AN:
152148
Hom.:
45976
Cov.:
34
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
GnomAD3 exomes
AF:
0.783
AC:
196774
AN:
251254
Hom.:
77192
AF XY:
0.786
AC XY:
106697
AN XY:
135814
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 SAS exome
AF:
0.842
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.:
45
AF XY:
0.775
AC XY:
562718
AN XY:
726450
show subpopulations
Gnomad4 AFR exome
AF:
0.787
Gnomad4 AMR exome
AF:
0.745
Gnomad4 ASJ exome
AF:
0.828
Gnomad4 EAS exome
AF:
0.858
Gnomad4 SAS exome
AF:
0.846
Gnomad4 FIN exome
AF:
0.752
Gnomad4 NFE exome
AF:
0.764
Gnomad4 OTH exome
AF:
0.777
GnomAD4 genome
AF:
0.777
AC:
118281
AN:
152266
Hom.:
46008
Cov.:
34
AF XY:
0.777
AC XY:
57849
AN XY:
74436
show subpopulations
Gnomad4 AFR
AF:
0.790
Gnomad4 AMR
AF:
0.741
Gnomad4 ASJ
AF:
0.818
Gnomad4 EAS
AF:
0.846
Gnomad4 SAS
AF:
0.837
Gnomad4 FIN
AF:
0.768
Gnomad4 NFE
AF:
0.765
Gnomad4 OTH
AF:
0.767
Alfa
AF:
0.773
Hom.:
107017
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:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Hereditary xanthinuria type 1 Benign:2
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabDec 05, 2021- -
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This 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
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxNov 13, 2018- -
Xanthinuria type II Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 31, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.48
Cadd
Benign
8.6
Dann
Benign
0.71

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1884725; hg19: chr2-31571786; API