rs1429372

Variant names:

• chr2-31403519-A-G
• rs1429372
• NM_000379.4:c.101-375T>C

Variant summary

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

The NM_000379.4(XDH):​c.101-375T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 151,762 control chromosomes in the GnomAD database, including 14,734 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 0.44 (14734 hom., cov: 31)
• Consequence: XDH NM_000379.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.861
• Publications: 5 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XDH	NM_000379.4	c.101-375T>C		intron_variant	Intron 2 of 35	ENST00000379416.4	NP_000370.2
XDH	XM_011533095.3	c.101-375T>C		intron_variant	Intron 2 of 35		XP_011531397.1
XDH	XM_011533096.3	c.101-375T>C		intron_variant	Intron 2 of 28		XP_011531398.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XDH	ENST00000379416.4	c.101-375T>C		intron_variant	Intron 2 of 35	1	NM_000379.4	ENSP00000368727.3

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66346 AN: 151644 Hom.: 14732 Cov.: 31

Gnomad AFR AF: 0.463

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.434

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

GnomAD4 genome AF: 0.437 AC: 66377 AN: 151762 Hom.: 14734 Cov.: 31 AF XY: 0.434 AC XY: 32190 AN XY: 74140

African (AFR) AF: 0.463 AC: 19128 AN: 41340

American (AMR) AF: 0.451 AC: 6885 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 1536 AN: 3466

East Asian (EAS) AF: 0.314 AC: 1619 AN: 5152

South Asian (SAS) AF: 0.359 AC: 1717 AN: 4784

European-Finnish (FIN) AF: 0.425 AC: 4472 AN: 10526

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.435 AC: 29552 AN: 67902

Other (OTH) AF: 0.429 AC: 907 AN: 2114

Alfa AF: 0.445 Hom.: 7021

Bravo AF: 0.443

Asia WGS AF: 0.313 AC: 1092 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.0020
DANN	Benign	0.73
PhyloP100		-0.86
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: rs1429372; hg19: chr2-31626385;