2-31340931-A-G

Position:

• chr2-31340931-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.983 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XDH	NM_000379.4	c.3585+398T>C		intron_variant		ENST00000379416.4	NP_000370.2
XDH	XM_011533095.3	c.3582+398T>C		intron_variant			XP_011531397.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XDH	ENST00000379416.4	c.3585+398T>C		intron_variant		1	NM_000379.4	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

Gnomad4 AFR AF: 0.991

Gnomad4 AMR AF: 0.961

Gnomad4 ASJ AF: 0.940

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.992

Gnomad4 FIN AF: 0.943

Gnomad4 NFE AF: 0.952

Gnomad4 OTH AF: 0.955

Alfa AF: 0.953 Hom.: 89287

Bravo AF: 0.969

Asia WGS AF: 0.995 AC: 3460 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

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: rs207444; hg19: chr2-31563797;