2-31380741-C-G

Variant names:

• chr2-31380741-C-G
• rs6718606
• NM_000379.4:c.1133-765G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000379.4(XDH):​c.1133-765G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 152,122 control chromosomes in the GnomAD database, including 2,188 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 0.16 (2188 hom., cov: 32)
• Consequence: XDH NM_000379.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• xanthinuria type I

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000379.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XDH	NM_000379.4	MANE Select	c.1133-765G>C		intron	N/A	NP_000370.2	P47989

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XDH	ENST00000379416.4	TSL:1 MANE Select	c.1133-765G>C		intron	N/A	ENSP00000368727.3	P47989
	XDH	ENST00000879520.1		c.1241-765G>C		intron	N/A	ENSP00000549579.1
	XDH	ENST00000879524.1		c.1133-765G>C		intron	N/A	ENSP00000549583.1

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25065 AN: 152004 Hom.: 2181 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.217

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.175

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

GnomAD4 genome AF: 0.165 AC: 25087 AN: 152122 Hom.: 2188 Cov.: 32 AF XY: 0.165 AC XY: 12279 AN XY: 74332

African (AFR) AF: 0.127 AC: 5290 AN: 41498

American (AMR) AF: 0.129 AC: 1971 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 411 AN: 3470

East Asian (EAS) AF: 0.161 AC: 831 AN: 5168

South Asian (SAS) AF: 0.188 AC: 903 AN: 4810

European-Finnish (FIN) AF: 0.207 AC: 2191 AN: 10564

Middle Eastern (MID) AF: 0.212 AC: 62 AN: 292

European-Non Finnish (NFE) AF: 0.190 AC: 12907 AN: 68008

Other (OTH) AF: 0.179 AC: 378 AN: 2116

Alfa AF: 0.0876 Hom.: 136

Bravo AF: 0.155

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.72
DANN	Benign	0.43
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6718606;

hg19: chr2-31603607;