2-31403519-A-G

Position:

• chr2-31403519-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000379416.4(XDH):​c.101-375T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 151,762 control chromosomes in the GnomAD database, including 14,734 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.44 (14734 hom., cov: 31)
• Consequence: XDH ENST00000379416.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.861

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XDH	NM_000379.4	c.101-375T>C		intron_variant		ENST00000379416.4	NP_000370.2
XDH	XM_011533095.3	c.101-375T>C		intron_variant			XP_011531397.1
XDH	XM_011533096.3	c.101-375T>C		intron_variant			XP_011531398.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XDH	ENST00000379416.4	c.101-375T>C		intron_variant		1	NM_000379.4	ENSP00000368727	P1

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66346 AN: 151644 Hom.: 14732 Cov.: 31

Gnomad AFR AF: 0.463

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.434

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

GnomAD4 genome AF: 0.437 AC: 66377 AN: 151762 Hom.: 14734 Cov.: 31 AF XY: 0.434 AC XY: 32190 AN XY: 74140

Gnomad4 AFR AF: 0.463

Gnomad4 AMR AF: 0.451

Gnomad4 ASJ AF: 0.443

Gnomad4 EAS AF: 0.314

Gnomad4 SAS AF: 0.359

Gnomad4 FIN AF: 0.425

Gnomad4 NFE AF: 0.435

Gnomad4 OTH AF: 0.429

Alfa AF: 0.445 Hom.: 5849

Bravo AF: 0.443

Asia WGS AF: 0.313 AC: 1092 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.0020
DANN	Benign	0.73

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: rs1429372; hg19: chr2-31626385;