Variant 2-31405880-G-A 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.100+27C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0439 in 1,613,112 control chromosomes in the GnomAD database, including 2,168 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.064 ( 453 hom., cov: 32)

Exomes 𝑓: 0.042 ( 1715 hom. )

Consequence

XDH
NM_000379.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.283

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=-0.84).

BP6

Variant 2-31405880-G-A is Benign according to our data. Variant chr2-31405880-G-A is described in ClinVar as [Benign]. Clinvar id is 1271082.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
XDH	NM_000379.4 linkuse as main transcript	c.100+27C>T	intron_variant	ENST00000379416.4	NP_000370.2	P47989
XDH	XM_011533095.3 linkuse as main transcript	c.100+27C>T	intron_variant		XP_011531397.1
XDH	XM_011533096.3 linkuse as main transcript	c.100+27C>T	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.100+27C>T		intron_variant		1	NM_000379.4	ENSP00000368727.3		P47989

Frequencies

GnomAD3 genomes

AF:

0.0635

AC:

9648

AN:

151924

Hom.:

451

Cov.:

show subpopulations

Gnomad AFR

AF:

0.122

Gnomad AMI

AF:

0.0604

Gnomad AMR

AF:

0.0443

Gnomad ASJ

AF:

0.141

Gnomad EAS

AF:

0.0540

Gnomad SAS

AF:

0.0619

Gnomad FIN

AF:

0.00841

Gnomad MID

AF:

0.0987

Gnomad NFE

AF:

0.0376

Gnomad OTH

AF:

0.0633

GnomAD3 exomes

AF:

0.0475

AC:

11931

AN:

251372

Hom.:

430

AF XY:

0.0473

AC XY:

6429

AN XY:

135844

show subpopulations

Gnomad AFR exome

AF:

0.124

Gnomad AMR exome

AF:

0.0333

Gnomad ASJ exome

AF:

0.122

Gnomad EAS exome

AF:

0.0569

Gnomad SAS exome

AF:

0.0608

Gnomad FIN exome

AF:

0.00989

Gnomad NFE exome

AF:

0.0361

Gnomad OTH exome

AF:

0.0501

GnomAD4 exome

AF:

0.0419

AC:

61155

AN:

1461070

Hom.:

1715

Cov.:

AF XY:

0.0424

AC XY:

30835

AN XY:

726910

show subpopulations

Gnomad4 AFR exome

AF:

0.128

Gnomad4 AMR exome

AF:

0.0344

Gnomad4 ASJ exome

AF:

0.124

Gnomad4 EAS exome

AF:

0.0616

Gnomad4 SAS exome

AF:

0.0581

Gnomad4 FIN exome

AF:

0.0108

Gnomad4 NFE exome

AF:

0.0363

Gnomad4 OTH exome

AF:

0.0522

GnomAD4 genome

AF:

0.0635

AC:

9659

AN:

152042

Hom.:

453

Cov.:

AF XY:

0.0622

AC XY:

4620

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.122

Gnomad4 AMR

AF:

0.0443

Gnomad4 ASJ

AF:

0.141

Gnomad4 EAS

AF:

0.0534

Gnomad4 SAS

AF:

0.0621

Gnomad4 FIN

AF:

0.00841

Gnomad4 NFE

AF:

0.0376

Gnomad4 OTH

AF:

0.0640

Alfa

AF:

0.0588

Hom.:

113

Bravo

AF:

0.0682

Asia WGS

AF:

0.0740

AC:

259

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	Jun 16, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

9.0

DANN

Benign

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