rs206801

chr2-31405880-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000379.4(XDH):c.100+27C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0439 in 1,613,112 control chromosomes in the GnomAD database, including 2,168 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.064 (453 hom., cov: 32)
  • Exomes 𝑓: 0.042 (1715 hom.)
• Consequence: XDH NM_000379.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.283

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 2-31405880-G-A is Benign according to our data. Variant chr2-31405880-G-A is described in ClinVar as [Benign]. Clinvar id is 1271082.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XDH	NM_000379.4	c.100+27C>T		intron_variant		ENST00000379416.4
XDH	XM_011533095.3	c.100+27C>T		intron_variant
XDH	XM_011533096.3	c.100+27C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XDH	ENST00000379416.4	c.100+27C>T		intron_variant		1	NM_000379.4	P1

Frequencies

GnomAD3 genomes AF: 0.0635 AC: 9648 AN: 151924 Hom.: 451 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.0604

Gnomad AMR AF: 0.0443

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.0540

Gnomad SAS AF: 0.0619

Gnomad FIN AF: 0.00841

Gnomad MID AF: 0.0987

Gnomad NFE AF: 0.0376

Gnomad OTH AF: 0.0633

GnomAD3 exomes AF: 0.0475 AC: 11931 AN: 251372 Hom.: 430 AF XY: 0.0473 AC XY: 6429 AN XY: 135844

Gnomad AFR exome AF: 0.124

Gnomad AMR exome AF: 0.0333

Gnomad ASJ exome AF: 0.122

Gnomad EAS exome AF: 0.0569

Gnomad SAS exome AF: 0.0608

Gnomad FIN exome AF: 0.00989

Gnomad NFE exome AF: 0.0361

Gnomad OTH exome AF: 0.0501

GnomAD4 exome AF: 0.0419 AC: 61155 AN: 1461070 Hom.: 1715 Cov.: 31 AF XY: 0.0424 AC XY: 30835 AN XY: 726910

Gnomad4 AFR exome AF: 0.128

Gnomad4 AMR exome AF: 0.0344

Gnomad4 ASJ exome AF: 0.124

Gnomad4 EAS exome AF: 0.0616

Gnomad4 SAS exome AF: 0.0581

Gnomad4 FIN exome AF: 0.0108

Gnomad4 NFE exome AF: 0.0363

Gnomad4 OTH exome AF: 0.0522

GnomAD4 genome AF: 0.0635 AC: 9659 AN: 152042 Hom.: 453 Cov.: 32 AF XY: 0.0622 AC XY: 4620 AN XY: 74292

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.0443

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.0534

Gnomad4 SAS AF: 0.0621

Gnomad4 FIN AF: 0.00841

Gnomad4 NFE AF: 0.0376

Gnomad4 OTH AF: 0.0640

Alfa AF: 0.0588 Hom.: 113

Bravo AF: 0.0682

Asia WGS AF: 0.0740 AC: 259 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	9.0
Dann	Benign	0.61

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: rs206801; hg19: chr2-31628746; COSMIC: COSV65147647;