chr2-31347510-T-C

Variant names:

• chr2-31347510-T-C
• rs1366813
• NM_000379.4:c.3276+12A>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.3276+12A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.768 in 1,613,232 control chromosomes in the GnomAD database, including 476,581 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.76 (43796 hom., cov: 33)
  • Exomes 𝑓: 0.77 (432785 hom.)
• Consequence: XDH NM_000379.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: -2.11
• Publications: 10 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, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 2-31347510-T-C is Benign according to our data. Variant chr2-31347510-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 191300.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000379.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XDH	NM_000379.4	MANE Select	c.3276+12A>G		intron	N/A	NP_000370.2	P47989

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XDH	ENST00000379416.4	TSL:1 MANE Select	c.3276+12A>G		intron	N/A	ENSP00000368727.3	P47989
	XDH	ENST00000879520.1		c.3384+12A>G		intron	N/A	ENSP00000549579.1
	XDH	ENST00000879524.1		c.3285+12A>G		intron	N/A	ENSP00000549583.1

Frequencies

GnomAD3 genomes AF: 0.758 AC: 115224 AN: 152080 Hom.: 43768 Cov.: 33

Gnomad AFR AF: 0.726

Gnomad AMI AF: 0.898

Gnomad AMR AF: 0.735

Gnomad ASJ AF: 0.814

Gnomad EAS AF: 0.847

Gnomad SAS AF: 0.830

Gnomad FIN AF: 0.764

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.765

Gnomad OTH AF: 0.760

GnomAD2 exomes AF: 0.776 AC: 194993 AN: 251154 AF XY: 0.780

Gnomad AFR exome AF: 0.724

Gnomad AMR exome AF: 0.742

Gnomad ASJ exome AF: 0.816

Gnomad EAS exome AF: 0.851

Gnomad FIN exome AF: 0.757

Gnomad NFE exome AF: 0.768

Gnomad OTH exome AF: 0.766

GnomAD4 exome AF: 0.769 AC: 1123791 AN: 1461034 Hom.: 432785 Cov.: 72 AF XY: 0.772 AC XY: 560782 AN XY: 726858

African (AFR) AF: 0.714 AC: 23893 AN: 33456

American (AMR) AF: 0.742 AC: 33168 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.822 AC: 21488 AN: 26132

East Asian (EAS) AF: 0.857 AC: 34015 AN: 39698

South Asian (SAS) AF: 0.837 AC: 72152 AN: 86206

European-Finnish (FIN) AF: 0.750 AC: 40052 AN: 53400

Middle Eastern (MID) AF: 0.785 AC: 4108 AN: 5236

European-Non Finnish (NFE) AF: 0.763 AC: 848398 AN: 1111886

Other (OTH) AF: 0.771 AC: 46517 AN: 60306

GnomAD4 genome AF: 0.758 AC: 115304 AN: 152198 Hom.: 43796 Cov.: 33 AF XY: 0.758 AC XY: 56436 AN XY: 74420

African (AFR) AF: 0.726 AC: 30145 AN: 41516

American (AMR) AF: 0.734 AC: 11238 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.814 AC: 2826 AN: 3470

East Asian (EAS) AF: 0.846 AC: 4361 AN: 5152

South Asian (SAS) AF: 0.829 AC: 4001 AN: 4826

European-Finnish (FIN) AF: 0.764 AC: 8102 AN: 10606

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

European-Non Finnish (NFE) AF: 0.765 AC: 51999 AN: 68010

Other (OTH) AF: 0.758 AC: 1600 AN: 2110

Alfa AF: 0.766 Hom.: 67504

Bravo AF: 0.756

Asia WGS AF: 0.792 AC: 2754 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	Hereditary xanthinuria type 1 (5)
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	2	Xanthinuria type II (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.14
DANN	Benign	0.37
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1366813; hg19: chr2-31570376;