rs17038412

Positions:

• chr2-31362349-T-A

Variant summary

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

The NM_000379.4(XDH):​c.2631+1809A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,146 control chromosomes in the GnomAD database, including 3,047 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 0.19 (3047 hom., cov: 32)
• Consequence: XDH NM_000379.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.633

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XDH	NM_000379.4	c.2631+1809A>T		intron_variant		ENST00000379416.4	NP_000370.2
XDH	XM_011533095.3	c.2628+1809A>T		intron_variant			XP_011531397.1
XDH	XM_011533096.3	c.2631+1809A>T		intron_variant			XP_011531398.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XDH	ENST00000379416.4	c.2631+1809A>T		intron_variant		1	NM_000379.4	ENSP00000368727	P1

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29389 AN: 152028 Hom.: 3046 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.213

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

GnomAD4 genome AF: 0.193 AC: 29399 AN: 152146 Hom.: 3047 Cov.: 32 AF XY: 0.194 AC XY: 14458 AN XY: 74390

Gnomad4 AFR AF: 0.207

Gnomad4 AMR AF: 0.161

Gnomad4 ASJ AF: 0.292

Gnomad4 EAS AF: 0.379

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.158

Gnomad4 NFE AF: 0.176

Gnomad4 OTH AF: 0.211

Alfa AF: 0.174 Hom.: 298

Bravo AF: 0.196

Asia WGS AF: 0.245 AC: 851 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	12
DANN	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
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

Publications

LitVar

Other links and lift over

dbSNP: rs17038412; hg19: chr2-31585215;