rs494852

Positions:

• chr2-31401970-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000379.4(XDH):​c.198-642G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 152,132 control chromosomes in the GnomAD database, including 3,519 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 0.20 (3519 hom., cov: 32)
• Consequence: XDH NM_000379.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.97

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XDH	NM_000379.4	c.198-642G>A		intron_variant		ENST00000379416.4	NP_000370.2
XDH	XM_011533095.3	c.198-642G>A		intron_variant			XP_011531397.1
XDH	XM_011533096.3	c.198-642G>A		intron_variant			XP_011531398.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XDH	ENST00000379416.4	c.198-642G>A		intron_variant		1	NM_000379.4	ENSP00000368727	P1

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30950 AN: 152012 Hom.: 3506 Cov.: 32

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.0995

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.204 AC: 31004 AN: 152132 Hom.: 3519 Cov.: 32 AF XY: 0.202 AC XY: 15018 AN XY: 74374

Gnomad4 AFR AF: 0.277

Gnomad4 AMR AF: 0.157

Gnomad4 ASJ AF: 0.267

Gnomad4 EAS AF: 0.0987

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.213

Alfa AF: 0.191 Hom.: 2862

Bravo AF: 0.206

Asia WGS AF: 0.175 AC: 609 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.015
DANN	Benign	0.32

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

Other links and lift over

dbSNP: rs494852; hg19: chr2-31624836;