2-31353768-C-T

Variant names:

• chr2-31353768-C-T
• rs13414618
• NM_000379.4:c.2632-3545G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000379.4(XDH):​c.2632-3545G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 152,022 control chromosomes in the GnomAD database, including 29,617 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 0.61 (29617 hom., cov: 32)
• Consequence: XDH NM_000379.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0110
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XDH	NM_000379.4	c.2632-3545G>A		intron_variant	Intron 24 of 35	ENST00000379416.4	NP_000370.2
XDH	XM_011533095.3	c.2629-3545G>A		intron_variant	Intron 24 of 35		XP_011531397.1
XDH	XM_011533096.3	c.2632-3545G>A		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.2632-3545G>A		intron_variant	Intron 24 of 35	1	NM_000379.4	ENSP00000368727.3

Frequencies

GnomAD3 genomes AF: 0.611 AC: 92846 AN: 151902 Hom.: 29628 Cov.: 32

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.839

Gnomad AMR AF: 0.637

Gnomad ASJ AF: 0.707

Gnomad EAS AF: 0.786

Gnomad SAS AF: 0.709

Gnomad FIN AF: 0.701

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.690

Gnomad OTH AF: 0.618

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

GnomAD4 genome AF: 0.611 AC: 92854 AN: 152022 Hom.: 29617 Cov.: 32 AF XY: 0.614 AC XY: 45591 AN XY: 74288

African (AFR) AF: 0.403 AC: 16678 AN: 41430

American (AMR) AF: 0.637 AC: 9724 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.707 AC: 2452 AN: 3468

East Asian (EAS) AF: 0.786 AC: 4062 AN: 5168

South Asian (SAS) AF: 0.708 AC: 3413 AN: 4822

European-Finnish (FIN) AF: 0.701 AC: 7410 AN: 10566

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.690 AC: 46890 AN: 67974

Other (OTH) AF: 0.615 AC: 1298 AN: 2112

Alfa AF: 0.649 Hom.: 5536

Bravo AF: 0.600

Asia WGS AF: 0.674 AC: 2344 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	0.86
DANN	Benign	0.18
PhyloP100		0.011
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: rs13414618; hg19: chr2-31576634;