chr2-31339546-C-T

Position:

chr2-31339546-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_000379.4(XDH):c.3717G>A(p.Glu1239Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0575 in 1,614,126 control chromosomes in the GnomAD database, including 2,861 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.052 ( 230 hom., cov: 32)

Exomes 𝑓: 0.058 ( 2631 hom. )

Consequence

XDH
NM_000379.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.552

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 2-31339546-C-T is Benign according to our data. Variant chr2-31339546-C-T is described in ClinVar as [Benign]. Clinvar id is 255970.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.552 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0631 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.3717G>A	p.Glu1239Glu	synonymous_variant	34/36	ENST00000379416.4	NP_000370.2	P47989
XDH	XM_011533095.3 linkuse as main transcript	c.3714G>A	p.Glu1238Glu	synonymous_variant	34/36		XP_011531397.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XDH	ENST00000379416.4 linkuse as main transcript	c.3717G>A	p.Glu1239Glu	synonymous_variant	34/36	1	NM_000379.4	ENSP00000368727.3		P47989

Frequencies

GnomAD3 genomes

AF:

0.0523

AC:

7958

AN:

152130

Hom.:

230

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0569

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0318

Gnomad ASJ

AF:

0.0438

Gnomad EAS

AF:

0.00541

Gnomad SAS

AF:

0.0694

Gnomad FIN

AF:

0.0425

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0591

Gnomad OTH

AF:

0.0483

GnomAD3 exomes

AF:

0.0491

AC:

12346

AN:

251484

Hom.:

379

AF XY:

0.0519

AC XY:

7055

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.0567

Gnomad AMR exome

AF:

0.0218

Gnomad ASJ exome

AF:

0.0425

Gnomad EAS exome

AF:

0.00375

Gnomad SAS exome

AF:

0.0733

Gnomad FIN exome

AF:

0.0381

Gnomad NFE exome

AF:

0.0596

Gnomad OTH exome

AF:

0.0525

GnomAD4 exome

AF:

0.0580

AC:

84827

AN:

1461878

Hom.:

2631

Cov.:

AF XY:

0.0587

AC XY:

42661

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.0593

Gnomad4 AMR exome

AF:

0.0232

Gnomad4 ASJ exome

AF:

0.0434

Gnomad4 EAS exome

AF:

0.00685

Gnomad4 SAS exome

AF:

0.0732

Gnomad4 FIN exome

AF:

0.0387

Gnomad4 NFE exome

AF:

0.0614

Gnomad4 OTH exome

AF:

0.0568

GnomAD4 genome

AF:

0.0523

AC:

7965

AN:

152248

Hom.:

230

Cov.:

AF XY:

0.0507

AC XY:

3777

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.0569

Gnomad4 AMR

AF:

0.0318

Gnomad4 ASJ

AF:

0.0438

Gnomad4 EAS

AF:

0.00542

Gnomad4 SAS

AF:

0.0692

Gnomad4 FIN

AF:

0.0425

Gnomad4 NFE

AF:

0.0591

Gnomad4 OTH

AF:

0.0483

Alfa

AF:

0.0570

Hom.:

510

Bravo

AF:

0.0510

Asia WGS

AF:

0.0560

AC:

194

AN:

3478

EpiCase

AF:

0.0595

EpiControl

AF:

0.0607

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	Mar 07, 2020	- -

Hereditary xanthinuria type 1

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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. -
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

BayesDel_noAF

Benign

-0.35

CADD

Benign

6.6

DANN

Benign

0.56

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