rs1346644

chr2-31403179-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.101-35C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 1,609,170 control chromosomes in the GnomAD database, including 17,428 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (1619 hom., cov: 32)
  • Exomes 𝑓: 0.14 (15809 hom.)
• Consequence: XDH NM_000379.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.662

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=-0.66).
• BP6: Variant 2-31403179-G-C is Benign according to our data. Variant chr2-31403179-G-C is described in ClinVar as [Benign]. Clinvar id is 1267257.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XDH	NM_000379.4	c.101-35C>G		intron_variant		ENST00000379416.4
XDH	XM_011533095.3	c.101-35C>G		intron_variant
XDH	XM_011533096.3	c.101-35C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XDH	ENST00000379416.4	c.101-35C>G		intron_variant		1	NM_000379.4	P1

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20934 AN: 152134 Hom.: 1614 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.0482

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.148

GnomAD3 exomes AF: 0.128 AC: 31835 AN: 249614 Hom.: 2274 AF XY: 0.132 AC XY: 17854 AN XY: 134962

Gnomad AFR exome AF: 0.147

Gnomad AMR exome AF: 0.0766

Gnomad ASJ exome AF: 0.126

Gnomad EAS exome AF: 0.0483

Gnomad SAS exome AF: 0.156

Gnomad FIN exome AF: 0.125

Gnomad NFE exome AF: 0.146

Gnomad OTH exome AF: 0.129

GnomAD4 exome AF: 0.144 AC: 209289 AN: 1456918 Hom.: 15809 Cov.: 29 AF XY: 0.144 AC XY: 104653 AN XY: 724916

Gnomad4 AFR exome AF: 0.145

Gnomad4 AMR exome AF: 0.0806

Gnomad4 ASJ exome AF: 0.122

Gnomad4 EAS exome AF: 0.0671

Gnomad4 SAS exome AF: 0.158

Gnomad4 FIN exome AF: 0.123

Gnomad4 NFE exome AF: 0.149

Gnomad4 OTH exome AF: 0.143

GnomAD4 genome AF: 0.138 AC: 20965 AN: 152252 Hom.: 1619 Cov.: 32 AF XY: 0.137 AC XY: 10229 AN XY: 74458

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.113

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.0481

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.150

Alfa AF: 0.136 Hom.: 261

Bravo AF: 0.136

Asia WGS AF: 0.105 AC: 365 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

Aug 20, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
Cadd	Benign	14
Dann	Benign	0.76

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: rs1346644; hg19: chr2-31626045; COSMIC: COSV65151092;