rs17373411

Variant names:

• chr1-180672654-A-T
• rs17373411
• NM_004736.4:c.70-9706A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_004736.4(XPR1):​c.70-9706A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0393 in 152,284 control chromosomes in the GnomAD database, including 168 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 0.039 (168 hom., cov: 32)
• Consequence: XPR1 NM_004736.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.380
• Publications: 2 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=-0.64).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0393 (5986/152284) while in subpopulation NFE AF = 0.0478 (3249/67990). AF 95% confidence interval is 0.0464. There are 168 homozygotes in GnomAd4. There are 2922 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 5986 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XPR1	NM_004736.4	c.70-9706A>T		intron_variant	Intron 1 of 14	ENST00000367590.9	NP_004727.2
XPR1	NM_001135669.2	c.70-9706A>T		intron_variant	Intron 1 of 13		NP_001129141.1
XPR1	NM_001328662.2	c.70-9706A>T		intron_variant	Intron 1 of 10		NP_001315591.1
XPR1	NR_137330.2	n.250-9706A>T		intron_variant	Intron 1 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XPR1	ENST00000367590.9	c.70-9706A>T		intron_variant	Intron 1 of 14	1	NM_004736.4	ENSP00000356562.4
XPR1	ENST00000367589.3	c.70-9706A>T		intron_variant	Intron 1 of 13	1		ENSP00000356561.3

Frequencies

GnomAD3 genomes AF: 0.0394 AC: 5988 AN: 152166 Hom.: 168 Cov.: 32

Gnomad AFR AF: 0.0205

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0315

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0182

Gnomad FIN AF: 0.0747

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0478

Gnomad OTH AF: 0.0458

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

GnomAD4 genome AF: 0.0393 AC: 5986 AN: 152284 Hom.: 168 Cov.: 32 AF XY: 0.0392 AC XY: 2922 AN XY: 74460

African (AFR) AF: 0.0205 AC: 850 AN: 41564

American (AMR) AF: 0.0315 AC: 482 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 385 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.0180 AC: 87 AN: 4830

European-Finnish (FIN) AF: 0.0747 AC: 794 AN: 10624

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0478 AC: 3249 AN: 67990

Other (OTH) AF: 0.0454 AC: 96 AN: 2116

Alfa AF: 0.0448 Hom.: 24

Bravo AF: 0.0357

Asia WGS AF: 0.00639 AC: 22 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	3.7
DANN	Benign	0.83
PhyloP100		0.38
Mutation Taster		=100/0	polymorphism

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: rs17373411; hg19: chr1-180641790;