chr2-31365695-A-C

Variant names:

• chr2-31365695-A-C
• rs1429376
• NM_000379.4:c.2457-151T>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000379.4(XDH):​c.2457-151T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.748 in 980,700 control chromosomes in the GnomAD database, including 276,477 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.76 (43931 hom., cov: 32)
  • Exomes 𝑓: 0.75 (232546 hom.)
• Consequence: XDH NM_000379.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.385
• 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, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 2-31365695-A-C is Benign according to our data. Variant chr2-31365695-A-C is described in ClinVar as Benign. ClinVar VariationId is 1179718.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XDH	NM_000379.4	c.2457-151T>G		intron_variant	Intron 22 of 35	ENST00000379416.4	NP_000370.2
XDH	XM_011533095.3	c.2454-151T>G		intron_variant	Intron 22 of 35		XP_011531397.1
XDH	XM_011533096.3	c.2457-151T>G		intron_variant	Intron 22 of 28		XP_011531398.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XDH	ENST00000379416.4	c.2457-151T>G		intron_variant	Intron 22 of 35	1	NM_000379.4	ENSP00000368727.3

Frequencies

GnomAD3 genomes AF: 0.759 AC: 115414 AN: 151982 Hom.: 43904 Cov.: 32

Gnomad AFR AF: 0.793

Gnomad AMI AF: 0.829

Gnomad AMR AF: 0.731

Gnomad ASJ AF: 0.826

Gnomad EAS AF: 0.821

Gnomad SAS AF: 0.755

Gnomad FIN AF: 0.740

Gnomad MID AF: 0.704

Gnomad NFE AF: 0.740

Gnomad OTH AF: 0.748

GnomAD4 exome AF: 0.746 AC: 618388 AN: 828598 Hom.: 232546 AF XY: 0.747 AC XY: 322900 AN XY: 432296

African (AFR) AF: 0.791 AC: 16410 AN: 20734

American (AMR) AF: 0.725 AC: 26150 AN: 36080

Ashkenazi Jewish (ASJ) AF: 0.826 AC: 17514 AN: 21204

East Asian (EAS) AF: 0.854 AC: 29165 AN: 34168

South Asian (SAS) AF: 0.773 AC: 53342 AN: 69046

European-Finnish (FIN) AF: 0.724 AC: 33912 AN: 46852

Middle Eastern (MID) AF: 0.756 AC: 2214 AN: 2928

European-Non Finnish (NFE) AF: 0.735 AC: 410169 AN: 558160

Other (OTH) AF: 0.749 AC: 29512 AN: 39426

GnomAD4 genome AF: 0.759 AC: 115491 AN: 152102 Hom.: 43931 Cov.: 32 AF XY: 0.759 AC XY: 56429 AN XY: 74330

African (AFR) AF: 0.793 AC: 32926 AN: 41516

American (AMR) AF: 0.730 AC: 11161 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.826 AC: 2865 AN: 3470

East Asian (EAS) AF: 0.821 AC: 4229 AN: 5152

South Asian (SAS) AF: 0.755 AC: 3634 AN: 4814

European-Finnish (FIN) AF: 0.740 AC: 7825 AN: 10570

Middle Eastern (MID) AF: 0.718 AC: 211 AN: 294

European-Non Finnish (NFE) AF: 0.740 AC: 50316 AN: 67984

Other (OTH) AF: 0.745 AC: 1570 AN: 2108

Alfa AF: 0.748 Hom.: 188756

Bravo AF: 0.763

Asia WGS AF: 0.758 AC: 2638 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 13, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.6
DANN	Benign	0.30
PhyloP100		-0.39
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1429376; hg19: chr2-31588561;