rs17011368

Positions:

chr2-31368051-T-C

Variant summary

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

The NM_000379.4(XDH):c.2107A>G(p.Ile703Val) variant causes a missense change. The variant allele was found at a frequency of 0.0364 in 1,613,932 control chromosomes in the GnomAD database, including 1,453 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.055 ( 322 hom., cov: 32)

Exomes 𝑓: 0.034 ( 1131 hom. )

Consequence

XDH
NM_000379.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 3.64

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 (MetaRNN=0.0027359426).

BP6

Variant 2-31368051-T-C is Benign according to our data. Variant chr2-31368051-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 255966.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-31368051-T-C is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
XDH	NM_000379.4 linkuse as main transcript	c.2107A>G	p.Ile703Val	missense_variant	20/36	ENST00000379416.4	NP_000370.2
XDH	XM_011533095.3 linkuse as main transcript	c.2104A>G	p.Ile702Val	missense_variant	20/36		XP_011531397.1
XDH	XM_011533096.3 linkuse as main transcript	c.2107A>G	p.Ile703Val	missense_variant	20/29		XP_011531398.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XDH	ENST00000379416.4 linkuse as main transcript	c.2107A>G	p.Ile703Val	missense_variant	20/36	1	NM_000379.4	ENSP00000368727	P1

Frequencies

GnomAD3 genomes

AF:

0.0547

AC:

8320

AN:

152172

Hom.:

322

Cov.:

show subpopulations

Gnomad AFR

AF:

0.115

Gnomad AMI

AF:

0.00440

Gnomad AMR

AF:

0.0405

Gnomad ASJ

AF:

0.0605

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.0238

Gnomad FIN

AF:

0.0297

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0317

Gnomad OTH

AF:

0.0602

GnomAD3 exomes

AF:

0.0338

AC:

8510

AN:

251456

Hom.:

238

AF XY:

0.0331

AC XY:

4499

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.115

Gnomad AMR exome

AF:

0.0205

Gnomad ASJ exome

AF:

0.0517

Gnomad EAS exome

AF:

0.00174

Gnomad SAS exome

AF:

0.0284

Gnomad FIN exome

AF:

0.0316

Gnomad NFE exome

AF:

0.0320

Gnomad OTH exome

AF:

0.0309

GnomAD4 exome

AF:

0.0345

AC:

50423

AN:

1461642

Hom.:

1131

Cov.:

AF XY:

0.0340

AC XY:

24744

AN XY:

727136

show subpopulations

Gnomad4 AFR exome

AF:

0.119

Gnomad4 AMR exome

AF:

0.0215

Gnomad4 ASJ exome

AF:

0.0516

Gnomad4 EAS exome

AF:

0.000982

Gnomad4 SAS exome

AF:

0.0258

Gnomad4 FIN exome

AF:

0.0308

Gnomad4 NFE exome

AF:

0.0339

Gnomad4 OTH exome

AF:

0.0371

GnomAD4 genome

AF:

0.0547

AC:

8336

AN:

152290

Hom.:

322

Cov.:

AF XY:

0.0534

AC XY:

3976

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.115

Gnomad4 AMR

AF:

0.0404

Gnomad4 ASJ

AF:

0.0605

Gnomad4 EAS

AF:

0.00174

Gnomad4 SAS

AF:

0.0238

Gnomad4 FIN

AF:

0.0297

Gnomad4 NFE

AF:

0.0316

Gnomad4 OTH

AF:

0.0596

Alfa

AF:

0.0366

Hom.:

343

Bravo

AF:

0.0569

TwinsUK

AF:

0.0369

AC:

137

ALSPAC

AF:

0.0309

AC:

119

ESP6500AA

AF:

0.115

AC:

508

ESP6500EA

AF:

0.0342

AC:

294

ExAC

AF:

0.0351

AC:

4257

Asia WGS

AF:

0.0260

AC:

AN:

3478

EpiCase

AF:

0.0350

EpiControl

AF:

0.0366

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 16, 2020	This variant is associated with the following publications: (PMID: 27703193, 18300946) -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Hereditary xanthinuria type 1

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Xanthinuria type II

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.061

Eigen

Benign

0.076

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.87

MetaRNN

Benign

0.0027

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

MutationTaster

Benign

0.0000013

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.95

REVEL

Benign

0.073

Sift

Uncertain

0.016

Sift4G

Uncertain

0.058

Polyphen

0.013

Vest4

0.058

MPC

0.044

ClinPred

0.017

GERP RS

4.8

Varity_R

0.29

gMVP

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

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