2-31414049-A-G

Position:

• chr2-31414049-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.42+576T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.649 in 151,734 control chromosomes in the GnomAD database, including 32,426 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 0.65 (32426 hom., cov: 29)
• Consequence: XDH NM_000379.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.46

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XDH	NM_000379.4	c.42+576T>C		intron_variant		ENST00000379416.4	NP_000370.2
XDH	XM_011533095.3	c.42+576T>C		intron_variant			XP_011531397.1
XDH	XM_011533096.3	c.42+576T>C		intron_variant			XP_011531398.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XDH	ENST00000379416.4	c.42+576T>C		intron_variant		1	NM_000379.4	ENSP00000368727	P1

Frequencies

GnomAD3 genomes AF: 0.649 AC: 98349 AN: 151616 Hom.: 32386 Cov.: 29

Gnomad AFR AF: 0.731

Gnomad AMI AF: 0.692

Gnomad AMR AF: 0.603

Gnomad ASJ AF: 0.644

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.641

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.640

Gnomad OTH AF: 0.653

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

GnomAD4 genome AF: 0.649 AC: 98442 AN: 151734 Hom.: 32426 Cov.: 29 AF XY: 0.645 AC XY: 47850 AN XY: 74134

Gnomad4 AFR AF: 0.731

Gnomad4 AMR AF: 0.603

Gnomad4 ASJ AF: 0.644

Gnomad4 EAS AF: 0.363

Gnomad4 SAS AF: 0.525

Gnomad4 FIN AF: 0.641

Gnomad4 NFE AF: 0.640

Gnomad4 OTH AF: 0.651

Alfa AF: 0.638 Hom.: 40728

Bravo AF: 0.651

Asia WGS AF: 0.449 AC: 1562 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.12
DANN	Benign	0.51

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: rs206811; hg19: chr2-31636915;