NM_000379.4:c.2631+1375C>G

Variant names:

• chr2-31362783-G-C
• rs7574920
• NM_000379.4:c.2631+1375C>G

Variant summary

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

The NM_000379.4(XDH):​c.2631+1375C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 152,012 control chromosomes in the GnomAD database, including 14,656 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 0.42 (14656 hom., cov: 33)
• Consequence: XDH NM_000379.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.44
• Publications: 5 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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000379.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XDH	NM_000379.4	MANE Select	c.2631+1375C>G		intron	N/A	NP_000370.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XDH	ENST00000379416.4	TSL:1 MANE Select	c.2631+1375C>G		intron	N/A	ENSP00000368727.3

Frequencies

GnomAD3 genomes AF: 0.421 AC: 63885 AN: 151896 Hom.: 14660 Cov.: 33

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.639

Gnomad AMR AF: 0.483

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.292

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.405

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

GnomAD4 genome AF: 0.420 AC: 63882 AN: 152012 Hom.: 14656 Cov.: 33 AF XY: 0.422 AC XY: 31363 AN XY: 74302

African (AFR) AF: 0.222 AC: 9221 AN: 41460

American (AMR) AF: 0.483 AC: 7377 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1427 AN: 3468

East Asian (EAS) AF: 0.368 AC: 1897 AN: 5160

South Asian (SAS) AF: 0.475 AC: 2291 AN: 4820

European-Finnish (FIN) AF: 0.537 AC: 5664 AN: 10552

Middle Eastern (MID) AF: 0.279 AC: 81 AN: 290

European-Non Finnish (NFE) AF: 0.507 AC: 34488 AN: 67978

Other (OTH) AF: 0.405 AC: 853 AN: 2108

Alfa AF: 0.470 Hom.: 2252

Bravo AF: 0.409

Asia WGS AF: 0.415 AC: 1443 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.22
DANN	Benign	0.71
PhyloP100		-3.4
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: rs7574920; hg19: chr2-31585649;