rs3002121

Variant names:

• chr1-180794007-G-T
• rs3002121
• NM_004736.4:c.223+6153G>T

Variant summary

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

The NM_004736.4(XPR1):​c.223+6153G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 151,734 control chromosomes in the GnomAD database, including 3,012 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 0.18 (3012 hom., cov: 31)
• Consequence: XPR1 NM_004736.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57
• Publications: 1 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XPR1	NM_004736.4	c.223+6153G>T		intron_variant	Intron 3 of 14	ENST00000367590.9	NP_004727.2
XPR1	NM_001135669.2	c.223+6153G>T		intron_variant	Intron 3 of 13		NP_001129141.1
XPR1	NM_001328662.2	c.223+6153G>T		intron_variant	Intron 3 of 10		NP_001315591.1
XPR1	NR_137330.2	n.403+6153G>T		intron_variant	Intron 3 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XPR1	ENST00000367590.9	c.223+6153G>T		intron_variant	Intron 3 of 14	1	NM_004736.4	ENSP00000356562.4
XPR1	ENST00000367589.3	c.223+6153G>T		intron_variant	Intron 3 of 13	1		ENSP00000356561.3

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27643 AN: 151616 Hom.: 3012 Cov.: 31

Gnomad AFR AF: 0.0804

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.0538

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.182 AC: 27651 AN: 151734 Hom.: 3012 Cov.: 31 AF XY: 0.180 AC XY: 13316 AN XY: 74112

African (AFR) AF: 0.0803 AC: 3325 AN: 41392

American (AMR) AF: 0.158 AC: 2410 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 939 AN: 3466

East Asian (EAS) AF: 0.0539 AC: 279 AN: 5172

South Asian (SAS) AF: 0.215 AC: 1033 AN: 4802

European-Finnish (FIN) AF: 0.210 AC: 2210 AN: 10508

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.245 AC: 16591 AN: 67852

Other (OTH) AF: 0.222 AC: 468 AN: 2104

Alfa AF: 0.202 Hom.: 462

Bravo AF: 0.171

Asia WGS AF: 0.156 AC: 545 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.10
DANN	Benign	0.38
PhyloP100		-1.6
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: rs3002121; hg19: chr1-180763143; COSMIC: COSV62555604;