chr2-31365695-A-C

Position:

• chr2-31365695-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000379.4(XDH):​c.2457-151T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.748 in 980,700 control chromosomes in the GnomAD database, including 276,477 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.76 (43931 hom., cov: 32)
  • Exomes 𝑓: 0.75 (232546 hom.)
• Consequence: XDH NM_000379.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.385

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 2-31365695-A-C is Benign according to our data. Variant chr2-31365695-A-C is described in ClinVar as [Benign]. Clinvar id is 1179718.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XDH	NM_000379.4	c.2457-151T>G		intron_variant		ENST00000379416.4
XDH	XM_011533095.3	c.2454-151T>G		intron_variant
XDH	XM_011533096.3	c.2457-151T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XDH	ENST00000379416.4	c.2457-151T>G		intron_variant		1	NM_000379.4	P1

Frequencies

GnomAD3 genomes AF: 0.759 AC: 115414 AN: 151982 Hom.: 43904 Cov.: 32

Gnomad AFR AF: 0.793

Gnomad AMI AF: 0.829

Gnomad AMR AF: 0.731

Gnomad ASJ AF: 0.826

Gnomad EAS AF: 0.821

Gnomad SAS AF: 0.755

Gnomad FIN AF: 0.740

Gnomad MID AF: 0.704

Gnomad NFE AF: 0.740

Gnomad OTH AF: 0.748

GnomAD4 exome AF: 0.746 AC: 618388 AN: 828598 Hom.: 232546 AF XY: 0.747 AC XY: 322900 AN XY: 432296

Gnomad4 AFR exome AF: 0.791

Gnomad4 AMR exome AF: 0.725

Gnomad4 ASJ exome AF: 0.826

Gnomad4 EAS exome AF: 0.854

Gnomad4 SAS exome AF: 0.773

Gnomad4 FIN exome AF: 0.724

Gnomad4 NFE exome AF: 0.735

Gnomad4 OTH exome AF: 0.749

GnomAD4 genome AF: 0.759 AC: 115491 AN: 152102 Hom.: 43931 Cov.: 32 AF XY: 0.759 AC XY: 56429 AN XY: 74330

Gnomad4 AFR AF: 0.793

Gnomad4 AMR AF: 0.730

Gnomad4 ASJ AF: 0.826

Gnomad4 EAS AF: 0.821

Gnomad4 SAS AF: 0.755

Gnomad4 FIN AF: 0.740

Gnomad4 NFE AF: 0.740

Gnomad4 OTH AF: 0.745

Alfa AF: 0.745 Hom.: 84589

Bravo AF: 0.763

Asia WGS AF: 0.758 AC: 2638 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 13, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.6
DANN	Benign	0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1429376; hg19: chr2-31588561;