rs206849

Positions:

• chr2-31390383-A-G

Variant summary

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

The NM_000379.4(XDH):​c.496-2088T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 152,116 control chromosomes in the GnomAD database, including 32,146 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 0.64 (32146 hom., cov: 33)
• Consequence: XDH NM_000379.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.76

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 = 0.765 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XDH	NM_000379.4	c.496-2088T>C		intron_variant		ENST00000379416.4
XDH	XM_011533095.3	c.496-2088T>C		intron_variant
XDH	XM_011533096.3	c.496-2088T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XDH	ENST00000379416.4	c.496-2088T>C		intron_variant		1	NM_000379.4	P1

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97700 AN: 151998 Hom.: 32109 Cov.: 33

Gnomad AFR AF: 0.772

Gnomad AMI AF: 0.625

Gnomad AMR AF: 0.614

Gnomad ASJ AF: 0.710

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.585

Gnomad FIN AF: 0.561

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.601

Gnomad OTH AF: 0.654

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

GnomAD4 genome AF: 0.643 AC: 97793 AN: 152116 Hom.: 32146 Cov.: 33 AF XY: 0.640 AC XY: 47579 AN XY: 74340

Gnomad4 AFR AF: 0.772

Gnomad4 AMR AF: 0.614

Gnomad4 ASJ AF: 0.710

Gnomad4 EAS AF: 0.413

Gnomad4 SAS AF: 0.586

Gnomad4 FIN AF: 0.561

Gnomad4 NFE AF: 0.601

Gnomad4 OTH AF: 0.652

Alfa AF: 0.615 Hom.: 38016

Bravo AF: 0.652

Asia WGS AF: 0.493 AC: 1717 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.34
DANN	Benign	0.56

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: rs206849; hg19: chr2-31613249;