rs2073316

Variant names:

• chr2-31388163-G-A
• rs2073316
• NM_000379.4:c.564+64C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-31388163-G-A
• chr2-31388163-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000379.4(XDH):​c.564+64C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 1,564,950 control chromosomes in the GnomAD database, including 156,876 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (13735 hom., cov: 31)
  • Exomes 𝑓: 0.45 (143141 hom.)
• Consequence: XDH NM_000379.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.423
• Publications: 9 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, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 2-31388163-G-A is Benign according to our data. Variant chr2-31388163-G-A is described in ClinVar as Benign. ClinVar VariationId is 1178962.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.458 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.564+64C>T		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.564+64C>T		intron	N/A	ENSP00000368727.3	P47989
	XDH	ENST00000879520.1		c.628C>T	p.Arg210*	stop_gained	Exon 7 of 36	ENSP00000549579.1
	XDH	ENST00000879524.1		c.564+64C>T		intron	N/A	ENSP00000549583.1

Frequencies

GnomAD3 genomes AF: 0.421 AC: 63902 AN: 151762 Hom.: 13734 Cov.: 31

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.432

GnomAD4 exome AF: 0.446 AC: 630923 AN: 1413070 Hom.: 143141 AF XY: 0.443 AC XY: 312739 AN XY: 705626

African (AFR) AF: 0.349 AC: 11351 AN: 32500

American (AMR) AF: 0.444 AC: 19758 AN: 44456

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 10563 AN: 25802

East Asian (EAS) AF: 0.291 AC: 11493 AN: 39436

South Asian (SAS) AF: 0.356 AC: 30251 AN: 85074

European-Finnish (FIN) AF: 0.480 AC: 25534 AN: 53142

Middle Eastern (MID) AF: 0.427 AC: 2361 AN: 5532

European-Non Finnish (NFE) AF: 0.462 AC: 493889 AN: 1068394

Other (OTH) AF: 0.438 AC: 25723 AN: 58734

GnomAD4 genome AF: 0.421 AC: 63921 AN: 151880 Hom.: 13735 Cov.: 31 AF XY: 0.419 AC XY: 31132 AN XY: 74232

African (AFR) AF: 0.355 AC: 14710 AN: 41408

American (AMR) AF: 0.445 AC: 6795 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.404 AC: 1401 AN: 3470

East Asian (EAS) AF: 0.286 AC: 1467 AN: 5138

South Asian (SAS) AF: 0.342 AC: 1640 AN: 4800

European-Finnish (FIN) AF: 0.477 AC: 5034 AN: 10552

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.462 AC: 31411 AN: 67938

Other (OTH) AF: 0.427 AC: 901 AN: 2110

Alfa AF: 0.437 Hom.: 18424

Bravo AF: 0.417

Asia WGS AF: 0.283 AC: 986 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.7
DANN	Benign	0.41
PhyloP100		0.42
Mutation Taster		=20/80	disease causing

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: rs2073316; hg19: chr2-31611029; COSMIC: COSV65148312; COSMIC: COSV65148312;