chr2-31365571-C-T

Variant names:

• chr2-31365571-C-T
• rs17011353
• NM_000379.4:c.2457-27G>A

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.2457-27G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0288 in 1,613,606 control chromosomes in the GnomAD database, including 1,007 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.024 (83 hom., cov: 32)
  • Exomes 𝑓: 0.029 (924 hom.)
• Consequence: XDH NM_000379.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.400
• Publications: 7 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 2-31365571-C-T is Benign according to our data. Variant chr2-31365571-C-T is described in ClinVar as Benign. ClinVar VariationId is 1283317.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.109 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.2457-27G>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.2457-27G>A		intron	N/A	ENSP00000368727.3	P47989
	XDH	ENST00000879520.1		c.2565-27G>A		intron	N/A	ENSP00000549579.1
	XDH	ENST00000879524.1		c.2466-27G>A		intron	N/A	ENSP00000549583.1

Frequencies

GnomAD3 genomes AF: 0.0243 AC: 3694 AN: 152166 Hom.: 82 Cov.: 32

Gnomad AFR AF: 0.00741

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0200

Gnomad ASJ AF: 0.0239

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.0601

Gnomad FIN AF: 0.0123

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0277

Gnomad OTH AF: 0.0301

GnomAD2 exomes AF: 0.0334 AC: 8374 AN: 250772 AF XY: 0.0357

Gnomad AFR exome AF: 0.00622

Gnomad AMR exome AF: 0.0137

Gnomad ASJ exome AF: 0.0207

Gnomad EAS exome AF: 0.130

Gnomad FIN exome AF: 0.0106

Gnomad NFE exome AF: 0.0266

Gnomad OTH exome AF: 0.0343

GnomAD4 exome AF: 0.0293 AC: 42787 AN: 1461322 Hom.: 924 Cov.: 33 AF XY: 0.0300 AC XY: 21833 AN XY: 727038

African (AFR) AF: 0.00574 AC: 192 AN: 33464

American (AMR) AF: 0.0146 AC: 651 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0184 AC: 482 AN: 26130

East Asian (EAS) AF: 0.117 AC: 4647 AN: 39692

South Asian (SAS) AF: 0.0557 AC: 4801 AN: 86244

European-Finnish (FIN) AF: 0.0125 AC: 669 AN: 53414

Middle Eastern (MID) AF: 0.0388 AC: 223 AN: 5746

European-Non Finnish (NFE) AF: 0.0261 AC: 29024 AN: 1111540

Other (OTH) AF: 0.0348 AC: 2098 AN: 60370

GnomAD4 genome AF: 0.0242 AC: 3692 AN: 152284 Hom.: 83 Cov.: 32 AF XY: 0.0248 AC XY: 1844 AN XY: 74462

African (AFR) AF: 0.00741 AC: 308 AN: 41566

American (AMR) AF: 0.0200 AC: 306 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0239 AC: 83 AN: 3470

East Asian (EAS) AF: 0.117 AC: 605 AN: 5170

South Asian (SAS) AF: 0.0605 AC: 292 AN: 4824

European-Finnish (FIN) AF: 0.0123 AC: 131 AN: 10622

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0277 AC: 1886 AN: 68018

Other (OTH) AF: 0.0298 AC: 63 AN: 2114

Alfa AF: 0.0189 Hom.: 24

Bravo AF: 0.0227

Asia WGS AF: 0.0700 AC: 244 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	2.4
DANN	Benign	0.72
PhyloP100		-0.40
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: rs17011353; hg19: chr2-31588437; COSMIC: COSV65150499;