2-31401970-C-T

Variant names:

• chr2-31401970-C-T
• rs494852
• NM_000379.4:c.198-642G>A

Variant summary

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

The NM_000379.4(XDH):​c.198-642G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 152,132 control chromosomes in the GnomAD database, including 3,519 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 0.20 (3519 hom., cov: 32)
• Consequence: XDH NM_000379.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.97
• Publications: 8 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), Ambry Genetics, Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.272 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.198-642G>A		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.198-642G>A		intron	N/A	ENSP00000368727.3	P47989
	XDH	ENST00000879520.1		c.198-642G>A		intron	N/A	ENSP00000549579.1
	XDH	ENST00000879524.1		c.198-642G>A		intron	N/A	ENSP00000549583.1

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30950 AN: 152012 Hom.: 3506 Cov.: 32

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.0995

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.204 AC: 31004 AN: 152132 Hom.: 3519 Cov.: 32 AF XY: 0.202 AC XY: 15018 AN XY: 74374

African (AFR) AF: 0.277 AC: 11477 AN: 41480

American (AMR) AF: 0.157 AC: 2398 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 926 AN: 3470

East Asian (EAS) AF: 0.0987 AC: 510 AN: 5166

South Asian (SAS) AF: 0.222 AC: 1072 AN: 4822

European-Finnish (FIN) AF: 0.131 AC: 1389 AN: 10598

Middle Eastern (MID) AF: 0.276 AC: 80 AN: 290

European-Non Finnish (NFE) AF: 0.184 AC: 12495 AN: 67986

Other (OTH) AF: 0.213 AC: 450 AN: 2114

Alfa AF: 0.192 Hom.: 7596

Bravo AF: 0.206

Asia WGS AF: 0.175 AC: 609 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.015
DANN	Benign	0.32
PhyloP100		-2.0
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: rs494852;

hg19: chr2-31624836;