Variant chr2-31367919-C-G 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.2197+42G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 1,596,796 control chromosomes in the GnomAD database, including 71,814 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5434 hom., cov: 32)

Exomes 𝑓: 0.30 ( 66380 hom. )

Consequence

XDH
NM_000379.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.152

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=-0.81).

BP6

Variant 2-31367919-C-G is Benign according to our data. Variant chr2-31367919-C-G is described in ClinVar as [Benign]. Clinvar id is 1239092.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
XDH	NM_000379.4 linkuse as main transcript	c.2197+42G>C	intron_variant	ENST00000379416.4	NP_000370.2	P47989
XDH	XM_011533095.3 linkuse as main transcript	c.2194+42G>C	intron_variant		XP_011531397.1
XDH	XM_011533096.3 linkuse as main transcript	c.2197+42G>C	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.2197+42G>C		intron_variant		1	NM_000379.4	ENSP00000368727.3		P47989

Frequencies

GnomAD3 genomes

AF:

0.248

AC:

37642

AN:

151958

Hom.:

5435

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0893

Gnomad AMI

AF:

0.334

Gnomad AMR

AF:

0.320

Gnomad ASJ

AF:

0.236

Gnomad EAS

AF:

0.355

Gnomad SAS

AF:

0.363

Gnomad FIN

AF:

0.320

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.300

Gnomad OTH

AF:

0.250

GnomAD3 exomes

AF:

0.308

AC:

77411

AN:

251396

Hom.:

12694

AF XY:

0.309

AC XY:

41965

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.0854

Gnomad AMR exome

AF:

0.401

Gnomad ASJ exome

AF:

0.243

Gnomad EAS exome

AF:

0.357

Gnomad SAS exome

AF:

0.355

Gnomad FIN exome

AF:

0.306

Gnomad NFE exome

AF:

0.298

Gnomad OTH exome

AF:

0.286

GnomAD4 exome

AF:

0.299

AC:

432177

AN:

1444720

Hom.:

66380

Cov.:

AF XY:

0.301

AC XY:

216861

AN XY:

719958

show subpopulations

Gnomad4 AFR exome

AF:

0.0777

Gnomad4 AMR exome

AF:

0.393

Gnomad4 ASJ exome

AF:

0.243

Gnomad4 EAS exome

AF:

0.364

Gnomad4 SAS exome

AF:

0.352

Gnomad4 FIN exome

AF:

0.302

Gnomad4 NFE exome

AF:

0.298

Gnomad4 OTH exome

AF:

0.280

GnomAD4 genome

AF:

0.247

AC:

37635

AN:

152076

Hom.:

5434

Cov.:

AF XY:

0.253

AC XY:

18802

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0890

Gnomad4 AMR

AF:

0.320

Gnomad4 ASJ

AF:

0.236

Gnomad4 EAS

AF:

0.355

Gnomad4 SAS

AF:

0.362

Gnomad4 FIN

AF:

0.320

Gnomad4 NFE

AF:

0.300

Gnomad4 OTH

AF:

0.250

Alfa

AF:

0.271

Hom.:

1217

Bravo

AF:

0.240

Asia WGS

AF:

0.369

AC:

1281

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	Nov 13, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.7

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