rs1594160

Variant names:

• chr2-31356103-A-C
• rs1594160
• NM_000379.4:c.2632-5880T>G

Your query was ambiguous. Multiple possible variants found:

• chr2-31356103-A-C
• chr2-31356103-A-G
• chr2-31356103-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000379.4(XDH):​c.2632-5880T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.743 in 152,012 control chromosomes in the GnomAD database, including 42,012 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.74 (42012 hom., cov: 31)
• Consequence: XDH NM_000379.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.321
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XDH	NM_000379.4	c.2632-5880T>G		intron_variant	Intron 24 of 35	ENST00000379416.4	NP_000370.2
XDH	XM_011533095.3	c.2629-5880T>G		intron_variant	Intron 24 of 35		XP_011531397.1
XDH	XM_011533096.3	c.2632-5880T>G		intron_variant	Intron 24 of 28		XP_011531398.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XDH	ENST00000379416.4	c.2632-5880T>G		intron_variant	Intron 24 of 35	1	NM_000379.4	ENSP00000368727.3

Frequencies

GnomAD3 genomes AF: 0.743 AC: 112824 AN: 151896 Hom.: 41988 Cov.: 31

Gnomad AFR AF: 0.791

Gnomad AMI AF: 0.862

Gnomad AMR AF: 0.713

Gnomad ASJ AF: 0.778

Gnomad EAS AF: 0.849

Gnomad SAS AF: 0.735

Gnomad FIN AF: 0.706

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.716

Gnomad OTH AF: 0.726

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.743 AC: 112896 AN: 152012 Hom.: 42012 Cov.: 31 AF XY: 0.742 AC XY: 55135 AN XY: 74310

African (AFR) AF: 0.791 AC: 32776 AN: 41460

American (AMR) AF: 0.712 AC: 10878 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.778 AC: 2699 AN: 3470

East Asian (EAS) AF: 0.849 AC: 4381 AN: 5162

South Asian (SAS) AF: 0.734 AC: 3538 AN: 4820

European-Finnish (FIN) AF: 0.706 AC: 7466 AN: 10570

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.716 AC: 48657 AN: 67946

Other (OTH) AF: 0.723 AC: 1527 AN: 2112

Alfa AF: 0.733 Hom.: 68326

Bravo AF: 0.749

Asia WGS AF: 0.735 AC: 2555 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.3
DANN	Benign	0.55
PhyloP100		-0.32
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: rs1594160; hg19: chr2-31578969;