2-31340931-A-G

Variant names:

• chr2-31340931-A-G
• rs207444
• NM_000379.4:c.3585+398T>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.3585+398T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.966 in 152,256 control chromosomes in the GnomAD database, including 71,023 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 0.97 (71023 hom., cov: 32)
• Consequence: XDH NM_000379.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.326
• Publications: 10 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: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.983 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XDH	NM_000379.4	MANE Select	c.3585+398T>C		intron	N/A	NP_000370.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XDH	ENST00000379416.4	TSL:1 MANE Select	c.3585+398T>C		intron	N/A	ENSP00000368727.3

Frequencies

GnomAD3 genomes AF: 0.966 AC: 146924 AN: 152138 Hom.: 70962 Cov.: 32

Gnomad AFR AF: 0.991

Gnomad AMI AF: 0.984

Gnomad AMR AF: 0.961

Gnomad ASJ AF: 0.940

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.992

Gnomad FIN AF: 0.943

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.952

Gnomad OTH AF: 0.955

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

GnomAD4 genome AF: 0.966 AC: 147044 AN: 152256 Hom.: 71023 Cov.: 32 AF XY: 0.967 AC XY: 71949 AN XY: 74440

African (AFR) AF: 0.991 AC: 41176 AN: 41540

American (AMR) AF: 0.961 AC: 14709 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.940 AC: 3263 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5172 AN: 5172

South Asian (SAS) AF: 0.992 AC: 4783 AN: 4824

European-Finnish (FIN) AF: 0.943 AC: 10004 AN: 10604

Middle Eastern (MID) AF: 0.929 AC: 273 AN: 294

European-Non Finnish (NFE) AF: 0.952 AC: 64748 AN: 68024

Other (OTH) AF: 0.955 AC: 2019 AN: 2114

Alfa AF: 0.955 Hom.: 113650

Bravo AF: 0.969

Asia WGS AF: 0.995 AC: 3460 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.6
DANN	Benign	0.79
PhyloP100		-0.33
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

Other links and lift over

dbSNP: rs207444; hg19: chr2-31563797;