rs7574920

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XDH	NM_000379.4	c.2631+1375C>G		intron_variant	Intron 24 of 35	ENST00000379416.4	NP_000370.2
XDH	XM_011533095.3	c.2628+1375C>G		intron_variant	Intron 24 of 35		XP_011531397.1
XDH	XM_011533096.3	c.2631+1375C>G		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.2631+1375C>G		intron_variant	Intron 24 of 35	1	NM_000379.4	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

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.483

Gnomad4 ASJ AF: 0.411

Gnomad4 EAS AF: 0.368

Gnomad4 SAS AF: 0.475

Gnomad4 FIN AF: 0.537

Gnomad4 NFE AF: 0.507

Gnomad4 OTH AF: 0.405

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.22
DANN	Benign	0.71

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: rs7574920; hg19: chr2-31585649;