Variant rs1346644 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.662

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
XDH	NM_000379.4 linkuse as main transcript	c.101-35C>G	intron_variant	ENST00000379416.4	NP_000370.2
XDH	XM_011533095.3 linkuse as main transcript	c.101-35C>G	intron_variant		XP_011531397.1
XDH	XM_011533096.3 linkuse as main transcript	c.101-35C>G	intron_variant		XP_011531398.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XDH	ENST00000379416.4 linkuse as main transcript	c.101-35C>G		intron_variant		1	NM_000379.4	ENSP00000368727	P1

Frequencies

GnomAD3 genomes

AF:

0.138

AC:

20934

AN:

152134

Hom.:

1614

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.144

AC XY:

104653

AN XY:

724916

show subpopulations

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.:

AF XY:

0.137

AC XY:

10229

AN XY:

74458

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over