rs1429374

Positions:

• chr2-31349532-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000379.4(XDH):​c.2969+154T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.594 in 152,014 control chromosomes in the GnomAD database, including 28,793 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.59 (28793 hom., cov: 32)
• Consequence: XDH NM_000379.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.362

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 2-31349532-A-G is Benign according to our data. Variant chr2-31349532-A-G is described in ClinVar as [Benign]. Clinvar id is 1249198.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.753 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XDH	NM_000379.4	c.2969+154T>C		intron_variant		ENST00000379416.4	NP_000370.2
XDH	XM_011533095.3	c.2966+154T>C		intron_variant			XP_011531397.1
XDH	XM_011533096.3	c.2969+154T>C		intron_variant			XP_011531398.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XDH	ENST00000379416.4	c.2969+154T>C		intron_variant		1	NM_000379.4	ENSP00000368727	P1

Frequencies

GnomAD3 genomes AF: 0.594 AC: 90251 AN: 151896 Hom.: 28805 Cov.: 32

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.836

Gnomad AMR AF: 0.634

Gnomad ASJ AF: 0.713

Gnomad EAS AF: 0.773

Gnomad SAS AF: 0.723

Gnomad FIN AF: 0.707

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.612

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.594 AC: 90254 AN: 152014 Hom.: 28793 Cov.: 32 AF XY: 0.597 AC XY: 44363 AN XY: 74288

Gnomad4 AFR AF: 0.332

Gnomad4 AMR AF: 0.634

Gnomad4 ASJ AF: 0.713

Gnomad4 EAS AF: 0.773

Gnomad4 SAS AF: 0.721

Gnomad4 FIN AF: 0.707

Gnomad4 NFE AF: 0.695

Gnomad4 OTH AF: 0.609

Alfa AF: 0.636 Hom.: 3999

Bravo AF: 0.579

Asia WGS AF: 0.676 AC: 2349 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.6
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

Other links and lift over

dbSNP: rs1429374; hg19: chr2-31572398;