rs2073316

Positions:

• chr2-31388163-G-A
• chr2-31388163-G-C

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.564+64C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 1,564,950 control chromosomes in the GnomAD database, including 156,876 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.42 (13735 hom., cov: 31)
  • Exomes 𝑓: 0.45 (143141 hom.)
• Consequence: XDH NM_000379.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.423

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=-0.82).
• BP6: Variant 2-31388163-G-A is Benign according to our data. Variant chr2-31388163-G-A is described in ClinVar as [Benign]. Clinvar id is 1178962.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XDH	NM_000379.4	c.564+64C>T		intron_variant		ENST00000379416.4
XDH	XM_011533095.3	c.564+64C>T		intron_variant
XDH	XM_011533096.3	c.564+64C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XDH	ENST00000379416.4	c.564+64C>T		intron_variant		1	NM_000379.4	P1
XDH	ENST00000491727.5	n.107+64C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.421 AC: 63902 AN: 151762 Hom.: 13734 Cov.: 31

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.432

GnomAD4 exome AF: 0.446 AC: 630923 AN: 1413070 Hom.: 143141 AF XY: 0.443 AC XY: 312739 AN XY: 705626

Gnomad4 AFR exome AF: 0.349

Gnomad4 AMR exome AF: 0.444

Gnomad4 ASJ exome AF: 0.409

Gnomad4 EAS exome AF: 0.291

Gnomad4 SAS exome AF: 0.356

Gnomad4 FIN exome AF: 0.480

Gnomad4 NFE exome AF: 0.462

Gnomad4 OTH exome AF: 0.438

GnomAD4 genome AF: 0.421 AC: 63921 AN: 151880 Hom.: 13735 Cov.: 31 AF XY: 0.419 AC XY: 31132 AN XY: 74232

Gnomad4 AFR AF: 0.355

Gnomad4 AMR AF: 0.445

Gnomad4 ASJ AF: 0.404

Gnomad4 EAS AF: 0.286

Gnomad4 SAS AF: 0.342

Gnomad4 FIN AF: 0.477

Gnomad4 NFE AF: 0.462

Gnomad4 OTH AF: 0.427

Alfa AF: 0.436 Hom.: 13856

Bravo AF: 0.417

Asia WGS AF: 0.283 AC: 986 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

Nov 13, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.7
DANN	Benign	0.41

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: rs2073316; hg19: chr2-31611029; COSMIC: COSV65148312; COSMIC: COSV65148312;