rs2295475

Positions:

chr2-31366981-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000379.4(XDH):c.2211C>T(p.Ile737=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 1,614,036 control chromosomes in the GnomAD database, including 74,844 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5554 hom., cov: 34)

Exomes 𝑓: 0.30 ( 69290 hom. )

Consequence

XDH
NM_000379.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.294

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 2-31366981-G-A is Benign according to our data. Variant chr2-31366981-G-A is described in ClinVar as [Benign]. Clinvar id is 255967.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-31366981-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.294 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.34 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.2211C>T	p.Ile737=	synonymous_variant	21/36	ENST00000379416.4	NP_000370.2
XDH	XM_011533095.3 linkuse as main transcript	c.2208C>T	p.Ile736=	synonymous_variant	21/36		XP_011531397.1
XDH	XM_011533096.3 linkuse as main transcript	c.2211C>T	p.Ile737=	synonymous_variant	21/29		XP_011531398.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XDH	ENST00000379416.4 linkuse as main transcript	c.2211C>T	p.Ile737=	synonymous_variant	21/36	1	NM_000379.4	ENSP00000368727	P1

Frequencies

GnomAD3 genomes

AF:

0.250

AC:

38007

AN:

152120

Hom.:

5554

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0881

Gnomad AMI

AF:

0.334

Gnomad AMR

AF:

0.320

Gnomad ASJ

AF:

0.236

Gnomad EAS

AF:

0.345

Gnomad SAS

AF:

0.355

Gnomad FIN

AF:

0.321

Gnomad MID

AF:

0.223

Gnomad NFE

AF:

0.307

Gnomad OTH

AF:

0.249

GnomAD3 exomes

AF:

0.309

AC:

77569

AN:

251432

Hom.:

12720

AF XY:

0.310

AC XY:

42070

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.0823

Gnomad AMR exome

AF:

0.396

Gnomad ASJ exome

AF:

0.244

Gnomad EAS exome

AF:

0.342

Gnomad SAS exome

AF:

0.350

Gnomad FIN exome

AF:

0.309

Gnomad NFE exome

AF:

0.304

Gnomad OTH exome

AF:

0.286

GnomAD4 exome

AF:

0.304

AC:

444675

AN:

1461796

Hom.:

69290

Cov.:

AF XY:

0.306

AC XY:

222484

AN XY:

727184

show subpopulations

Gnomad4 AFR exome

AF:

0.0755

Gnomad4 AMR exome

AF:

0.388

Gnomad4 ASJ exome

AF:

0.243

Gnomad4 EAS exome

AF:

0.352

Gnomad4 SAS exome

AF:

0.347

Gnomad4 FIN exome

AF:

0.304

Gnomad4 NFE exome

AF:

0.306

Gnomad4 OTH exome

AF:

0.282

GnomAD4 genome

AF:

0.250

AC:

38002

AN:

152240

Hom.:

5554

Cov.:

AF XY:

0.254

AC XY:

18933

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0878

Gnomad4 AMR

AF:

0.320

Gnomad4 ASJ

AF:

0.236

Gnomad4 EAS

AF:

0.345

Gnomad4 SAS

AF:

0.354

Gnomad4 FIN

AF:

0.321

Gnomad4 NFE

AF:

0.307

Gnomad4 OTH

AF:

0.250

Alfa

AF:

0.293

Hom.:

15009

Bravo

AF:

0.242

Asia WGS

AF:

0.360

AC:

1251

AN:

3478

EpiCase

AF:

0.297

EpiControl

AF:

0.297

ClinVar

Significance: 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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 13, 2018	- -

Hereditary xanthinuria type 1

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Dec 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

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 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.015

DANN

Benign

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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