1-180763987-T-G

Variant names:

• chr1-180763987-T-G
• rs2331886
• NM_004736.4:c.122-23766T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004736.4(XPR1):​c.122-23766T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.765 in 152,172 control chromosomes in the GnomAD database, including 44,699 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 0.76 (44699 hom., cov: 33)
• Consequence: XPR1 NM_004736.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.79
• Publications: 7 publications found

Genes affected

XPR1 (HGNC:12827): (xenotropic and polytropic retrovirus receptor 1) The protein encoded by this gene is a receptor for the xenotropic and polytropic classes of murine leukemia viruses. The encoded protein is involved in phosphate homeostasis by mediating phosphate export from the cell. Defects in this gene have been associated with idiopathic basal ganglia calcification-6. [provided by RefSeq, Jun 2016]

XPR1 Gene-Disease associations (from GenCC):

• basal ganglia calcification, idiopathic, 6

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Illumina, Genomics England PanelApp, PanelApp Australia, Ambry Genetics
• bilateral striopallidodentate calcinosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.815 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XPR1	NM_004736.4	c.122-23766T>G		intron_variant	Intron 2 of 14	ENST00000367590.9	NP_004727.2
XPR1	NM_001135669.2	c.122-23766T>G		intron_variant	Intron 2 of 13		NP_001129141.1
XPR1	NM_001328662.2	c.122-23766T>G		intron_variant	Intron 2 of 10		NP_001315591.1
XPR1	NR_137330.2	n.302-23766T>G		intron_variant	Intron 2 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XPR1	ENST00000367590.9	c.122-23766T>G		intron_variant	Intron 2 of 14	1	NM_004736.4	ENSP00000356562.4
XPR1	ENST00000367589.3	c.122-23766T>G		intron_variant	Intron 2 of 13	1		ENSP00000356561.3

Frequencies

GnomAD3 genomes AF: 0.765 AC: 116250 AN: 152054 Hom.: 44659 Cov.: 33

Gnomad AFR AF: 0.822

Gnomad AMI AF: 0.655

Gnomad AMR AF: 0.764

Gnomad ASJ AF: 0.692

Gnomad EAS AF: 0.818

Gnomad SAS AF: 0.703

Gnomad FIN AF: 0.788

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.733

Gnomad OTH AF: 0.718

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

GnomAD4 genome AF: 0.765 AC: 116348 AN: 152172 Hom.: 44699 Cov.: 33 AF XY: 0.766 AC XY: 57004 AN XY: 74382

African (AFR) AF: 0.822 AC: 34150 AN: 41522

American (AMR) AF: 0.764 AC: 11683 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.692 AC: 2399 AN: 3468

East Asian (EAS) AF: 0.818 AC: 4234 AN: 5176

South Asian (SAS) AF: 0.703 AC: 3389 AN: 4820

European-Finnish (FIN) AF: 0.788 AC: 8347 AN: 10590

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.733 AC: 49845 AN: 67988

Other (OTH) AF: 0.715 AC: 1510 AN: 2112

Alfa AF: 0.738 Hom.: 25989

Bravo AF: 0.766

Asia WGS AF: 0.744 AC: 2584 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.55
DANN	Benign	0.68
PhyloP100		-1.8
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: rs2331886; hg19: chr1-180733123;