Variant rs207454 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.3352-30A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,612,780 control chromosomes in the GnomAD database, including 11,223 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.16 ( 2920 hom., cov: 32)

Exomes 𝑓: 0.098 ( 8303 hom. )

Consequence

XDH
NM_000379.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.583

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

This place is a probable branch point but likely benign (scored 3 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 2-31344766-T-G is Benign according to our data. Variant chr2-31344766-T-G is described in ClinVar as [Benign]. Clinvar id is 1234846.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XDH	NM_000379.4 linkuse as main transcript	c.3352-30A>C		intron_variant		ENST00000379416.4	NP_000370.2	P47989
XDH	XM_011533095.3 linkuse as main transcript	c.3349-30A>C		intron_variant			XP_011531397.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XDH	ENST00000379416.4 linkuse as main transcript	c.3352-30A>C		intron_variant		1	NM_000379.4	ENSP00000368727.3		P47989

Frequencies

GnomAD3 genomes

AF:

0.159

AC:

24236

AN:

151980

Hom.:

2912

Cov.:

show subpopulations

Gnomad AFR

AF:

0.331

Gnomad AMI

AF:

0.135

Gnomad AMR

AF:

0.108

Gnomad ASJ

AF:

0.130

Gnomad EAS

AF:

0.156

Gnomad SAS

AF:

0.134

Gnomad FIN

AF:

0.0695

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0857

Gnomad OTH

AF:

0.143

GnomAD3 exomes

AF:

0.115

AC:

28593

AN:

249104

Hom.:

2090

AF XY:

0.111

AC XY:

14957

AN XY:

134688

show subpopulations

Gnomad AFR exome

AF:

0.337

Gnomad AMR exome

AF:

0.0851

Gnomad ASJ exome

AF:

0.141

Gnomad EAS exome

AF:

0.157

Gnomad SAS exome

AF:

0.128

Gnomad FIN exome

AF:

0.0744

Gnomad NFE exome

AF:

0.0876

Gnomad OTH exome

AF:

0.106

GnomAD4 exome

AF:

0.0975

AC:

142456

AN:

1460682

Hom.:

8303

Cov.:

AF XY:

0.0975

AC XY:

70842

AN XY:

726612

show subpopulations

Gnomad4 AFR exome

AF:

0.334

Gnomad4 AMR exome

AF:

0.0862

Gnomad4 ASJ exome

AF:

0.138

Gnomad4 EAS exome

AF:

0.154

Gnomad4 SAS exome

AF:

0.126

Gnomad4 FIN exome

AF:

0.0757

Gnomad4 NFE exome

AF:

0.0858

Gnomad4 OTH exome

AF:

0.113

GnomAD4 genome

AF:

0.160

AC:

24266

AN:

152098

Hom.:

2920

Cov.:

AF XY:

0.157

AC XY:

11646

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.330

Gnomad4 AMR

AF:

0.109

Gnomad4 ASJ

AF:

0.130

Gnomad4 EAS

AF:

0.156

Gnomad4 SAS

AF:

0.133

Gnomad4 FIN

AF:

0.0695

Gnomad4 NFE

AF:

0.0857

Gnomad4 OTH

AF:

0.141

Alfa

AF:

0.122

Hom.:

551

Bravo

AF:

0.170

Asia WGS

AF:

0.146

AC:

508

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	Nov 13, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

2.1

DANN

Benign

0.81

BranchPoint Hunter

3.0

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