1-180788492-T-C

Variant names:

• chr1-180788492-T-C
• rs7544774
• NM_004736.4:c.223+638T>C

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+638T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 151,960 control chromosomes in the GnomAD database, including 9,181 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 0.34 (9181 hom., cov: 31)
• Consequence: XPR1 NM_004736.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.477
• Publications: 3 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XPR1	NM_004736.4	c.223+638T>C		intron_variant	Intron 3 of 14	ENST00000367590.9	NP_004727.2
XPR1	NM_001135669.2	c.223+638T>C		intron_variant	Intron 3 of 13		NP_001129141.1
XPR1	NM_001328662.2	c.223+638T>C		intron_variant	Intron 3 of 10		NP_001315591.1
XPR1	NR_137330.2	n.403+638T>C		intron_variant	Intron 3 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XPR1	ENST00000367590.9	c.223+638T>C		intron_variant	Intron 3 of 14	1	NM_004736.4	ENSP00000356562.4
XPR1	ENST00000367589.3	c.223+638T>C		intron_variant	Intron 3 of 13	1		ENSP00000356561.3

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51770 AN: 151842 Hom.: 9175 Cov.: 31

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.329

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

GnomAD4 genome AF: 0.341 AC: 51799 AN: 151960 Hom.: 9181 Cov.: 31 AF XY: 0.341 AC XY: 25309 AN XY: 74262

African (AFR) AF: 0.272 AC: 11282 AN: 41452

American (AMR) AF: 0.347 AC: 5301 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.341 AC: 1182 AN: 3466

East Asian (EAS) AF: 0.174 AC: 898 AN: 5174

South Asian (SAS) AF: 0.340 AC: 1636 AN: 4810

European-Finnish (FIN) AF: 0.413 AC: 4354 AN: 10534

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

European-Non Finnish (NFE) AF: 0.383 AC: 26011 AN: 67934

Other (OTH) AF: 0.325 AC: 681 AN: 2098

Alfa AF: 0.354 Hom.: 2032

Bravo AF: 0.332

Asia WGS AF: 0.300 AC: 1042 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	14
DANN	Benign	0.77
PhyloP100		0.48
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: rs7544774; hg19: chr1-180757628;