2-31353208-C-G

Variant names:

• chr2-31353208-C-G
• rs1896846
• NM_000379.4:c.2632-2985G>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.2632-2985G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.744 in 152,036 control chromosomes in the GnomAD database, including 42,205 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 0.74 (42205 hom., cov: 32)
• Consequence: XDH NM_000379.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 1 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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XDH	NM_000379.4	c.2632-2985G>C		intron_variant	Intron 24 of 35	ENST00000379416.4	NP_000370.2
XDH	XM_011533095.3	c.2629-2985G>C		intron_variant	Intron 24 of 35		XP_011531397.1
XDH	XM_011533096.3	c.2632-2985G>C		intron_variant	Intron 24 of 28		XP_011531398.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XDH	ENST00000379416.4	c.2632-2985G>C		intron_variant	Intron 24 of 35	1	NM_000379.4	ENSP00000368727.3

Frequencies

GnomAD3 genomes AF: 0.744 AC: 113058 AN: 151918 Hom.: 42178 Cov.: 32

Gnomad AFR AF: 0.791

Gnomad AMI AF: 0.862

Gnomad AMR AF: 0.714

Gnomad ASJ AF: 0.782

Gnomad EAS AF: 0.851

Gnomad SAS AF: 0.750

Gnomad FIN AF: 0.708

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.717

Gnomad OTH AF: 0.730

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

GnomAD4 genome AF: 0.744 AC: 113134 AN: 152036 Hom.: 42205 Cov.: 32 AF XY: 0.744 AC XY: 55311 AN XY: 74342

African (AFR) AF: 0.791 AC: 32783 AN: 41432

American (AMR) AF: 0.714 AC: 10908 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.782 AC: 2714 AN: 3470

East Asian (EAS) AF: 0.851 AC: 4408 AN: 5180

South Asian (SAS) AF: 0.749 AC: 3606 AN: 4814

European-Finnish (FIN) AF: 0.708 AC: 7479 AN: 10564

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.717 AC: 48730 AN: 67980

Other (OTH) AF: 0.726 AC: 1530 AN: 2106

Alfa AF: 0.656 Hom.: 2119

Bravo AF: 0.750

Asia WGS AF: 0.751 AC: 2613 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.9
DANN	Benign	0.55
PhyloP100		-1.1
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: rs1896846; hg19: chr2-31576074;