2-31414049-A-G

Variant names:

• chr2-31414049-A-G
• rs206811
• NM_000379.4:c.42+576T>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.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
• Publications: 8 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=-0.89).
• 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 rank	MANE	Protein	UniProt
XDH	NM_000379.4	c.42+576T>C		intron_variant	Intron 1 of 35	ENST00000379416.4	NP_000370.2
XDH	XM_011533095.3	c.42+576T>C		intron_variant	Intron 1 of 35		XP_011531397.1
XDH	XM_011533096.3	c.42+576T>C		intron_variant	Intron 1 of 28		XP_011531398.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XDH	ENST00000379416.4	c.42+576T>C		intron_variant	Intron 1 of 35	1	NM_000379.4	ENSP00000368727.3

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

African (AFR) AF: 0.731 AC: 30212 AN: 41328

American (AMR) AF: 0.603 AC: 9194 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.644 AC: 2236 AN: 3470

East Asian (EAS) AF: 0.363 AC: 1860 AN: 5126

South Asian (SAS) AF: 0.525 AC: 2526 AN: 4808

European-Finnish (FIN) AF: 0.641 AC: 6746 AN: 10518

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.640 AC: 43461 AN: 67928

Other (OTH) AF: 0.651 AC: 1370 AN: 2106

Alfa AF: 0.641 Hom.: 52461

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
PhyloP100		-3.5
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: rs206811; hg19: chr2-31636915;