rs13415401

Variant names:

• chr2-31348375-G-C
• rs13415401
• NM_000379.4:c.3052-12C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000379.4(XDH):​c.3052-12C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.766 in 1,613,090 control chromosomes in the GnomAD database, including 473,636 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.75 (42913 hom., cov: 33)
  • Exomes 𝑓: 0.77 (430723 hom.)
• Consequence: XDH NM_000379.4 intron
• Scores: Splicing: ADA: 0.0001073
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.363
• Publications: 12 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 2-31348375-G-C is Benign according to our data. Variant chr2-31348375-G-C is described in ClinVar as Benign. ClinVar VariationId is 255969.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XDH	NM_000379.4	c.3052-12C>G		intron_variant	Intron 27 of 35	ENST00000379416.4	NP_000370.2
XDH	XM_011533095.3	c.3049-12C>G		intron_variant	Intron 27 of 35		XP_011531397.1
XDH	XM_011533096.3	c.3052-12C>G		intron_variant	Intron 27 of 28		XP_011531398.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XDH	ENST00000379416.4	c.3052-12C>G		intron_variant	Intron 27 of 35	1	NM_000379.4	ENSP00000368727.3

Frequencies

GnomAD3 genomes AF: 0.750 AC: 114019 AN: 152026 Hom.: 42897 Cov.: 33

Gnomad AFR AF: 0.701

Gnomad AMI AF: 0.898

Gnomad AMR AF: 0.732

Gnomad ASJ AF: 0.815

Gnomad EAS AF: 0.845

Gnomad SAS AF: 0.816

Gnomad FIN AF: 0.768

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.764

Gnomad OTH AF: 0.751

GnomAD2 exomes AF: 0.773 AC: 193212 AN: 249888 AF XY: 0.777

Gnomad AFR exome AF: 0.700

Gnomad AMR exome AF: 0.740

Gnomad ASJ exome AF: 0.816

Gnomad EAS exome AF: 0.849

Gnomad FIN exome AF: 0.759

Gnomad NFE exome AF: 0.767

Gnomad OTH exome AF: 0.763

GnomAD4 exome AF: 0.767 AC: 1121091 AN: 1460946 Hom.: 430723 Cov.: 37 AF XY: 0.770 AC XY: 559291 AN XY: 726770

African (AFR) AF: 0.689 AC: 23060 AN: 33462

American (AMR) AF: 0.740 AC: 33040 AN: 44648

Ashkenazi Jewish (ASJ) AF: 0.822 AC: 21487 AN: 26128

East Asian (EAS) AF: 0.856 AC: 33975 AN: 39688

South Asian (SAS) AF: 0.827 AC: 71257 AN: 86184

European-Finnish (FIN) AF: 0.752 AC: 40121 AN: 53376

Middle Eastern (MID) AF: 0.785 AC: 4524 AN: 5766

European-Non Finnish (NFE) AF: 0.762 AC: 847288 AN: 1111348

Other (OTH) AF: 0.768 AC: 46339 AN: 60346

GnomAD4 genome AF: 0.750 AC: 114084 AN: 152144 Hom.: 42913 Cov.: 33 AF XY: 0.751 AC XY: 55839 AN XY: 74372

African (AFR) AF: 0.701 AC: 29091 AN: 41498

American (AMR) AF: 0.731 AC: 11188 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.815 AC: 2825 AN: 3468

East Asian (EAS) AF: 0.844 AC: 4369 AN: 5174

South Asian (SAS) AF: 0.816 AC: 3931 AN: 4818

European-Finnish (FIN) AF: 0.768 AC: 8123 AN: 10582

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.764 AC: 51944 AN: 67990

Other (OTH) AF: 0.749 AC: 1581 AN: 2112

Alfa AF: 0.763 Hom.: 8119

Bravo AF: 0.748

Asia WGS AF: 0.770 AC: 2680 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

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

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

- -

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	-0.83
CADD	Benign	14
DANN	Benign	0.47
PhyloP100		0.36
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00011
dbscSNV1_RF	Benign	0.066
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs13415401; hg19: chr2-31571241; COSMIC: COSV105313738;