Variant 2-31377280-T-C 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.1243-43A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 1,611,930 control chromosomes in the GnomAD database, including 423,535 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.74 ( 41600 hom., cov: 31)

Exomes 𝑓: 0.72 ( 381935 hom. )

Consequence

XDH
NM_000379.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.129

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 2-31377280-T-C is Benign according to our data. Variant chr2-31377280-T-C is described in ClinVar as [Benign]. Clinvar id is 1249715.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.776 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
XDH	NM_000379.4 linkuse as main transcript	c.1243-43A>G	intron_variant	ENST00000379416.4	NP_000370.2
XDH	XM_011533095.3 linkuse as main transcript	c.1243-43A>G	intron_variant		XP_011531397.1
XDH	XM_011533096.3 linkuse as main transcript	c.1243-43A>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.1243-43A>G		intron_variant		1	NM_000379.4	ENSP00000368727	P1

Frequencies

GnomAD3 genomes

AF:

0.739

AC:

112283

AN:

151948

Hom.:

41563

Cov.:

show subpopulations

Gnomad AFR

AF:

0.783

Gnomad AMI

AF:

0.800

Gnomad AMR

AF:

0.702

Gnomad ASJ

AF:

0.766

Gnomad EAS

AF:

0.756

Gnomad SAS

AF:

0.731

Gnomad FIN

AF:

0.739

Gnomad MID

AF:

0.615

Gnomad NFE

AF:

0.719

Gnomad OTH

AF:

0.718

GnomAD3 exomes

AF:

0.730

AC:

182454

AN:

249966

Hom.:

66652

AF XY:

0.729

AC XY:

98596

AN XY:

135222

show subpopulations

Gnomad AFR exome

AF:

0.784

Gnomad AMR exome

AF:

0.703

Gnomad ASJ exome

AF:

0.770

Gnomad EAS exome

AF:

0.754

Gnomad SAS exome

AF:

0.743

Gnomad FIN exome

AF:

0.730

Gnomad NFE exome

AF:

0.721

Gnomad OTH exome

AF:

0.707

GnomAD4 exome

AF:

0.723

AC:

1055204

AN:

1459862

Hom.:

381935

Cov.:

AF XY:

0.723

AC XY:

524937

AN XY:

726318

show subpopulations

Gnomad4 AFR exome

AF:

0.782

Gnomad4 AMR exome

AF:

0.702

Gnomad4 ASJ exome

AF:

0.769

Gnomad4 EAS exome

AF:

0.770

Gnomad4 SAS exome

AF:

0.744

Gnomad4 FIN exome

AF:

0.723

Gnomad4 NFE exome

AF:

0.718

Gnomad4 OTH exome

AF:

0.719

GnomAD4 genome

AF:

0.739

AC:

112365

AN:

152068

Hom.:

41600

Cov.:

AF XY:

0.739

AC XY:

54884

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.783

Gnomad4 AMR

AF:

0.702

Gnomad4 ASJ

AF:

0.766

Gnomad4 EAS

AF:

0.757

Gnomad4 SAS

AF:

0.730

Gnomad4 FIN

AF:

0.739

Gnomad4 NFE

AF:

0.719

Gnomad4 OTH

AF:

0.713

Alfa

AF:

0.700

Hom.:

4685

Bravo

AF:

0.740

Asia WGS

AF:

0.718

AC:

2497

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

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:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.0

DANN

Benign

0.48

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