NM_004736.4:c.1501+8491A>T

Variant names:

• chr1-180845207-A-T
• rs1533422
• NM_004736.4:c.1501+8491A>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.1501+8491A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 152,006 control chromosomes in the GnomAD database, including 9,098 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 (9098 hom., cov: 32)
• Consequence: XPR1 NM_004736.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24
• 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: Genomics England PanelApp, Illumina, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004736.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XPR1	NM_004736.4	MANE Select	c.1501+8491A>T		intron	N/A	NP_004727.2
	XPR1	NM_001135669.2		c.1306+10162A>T		intron	N/A	NP_001129141.1	Q9UBH6-2
	XPR1	NR_137330.2		n.1315-18501A>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XPR1	ENST00000367590.9	TSL:1 MANE Select	c.1501+8491A>T		intron	N/A	ENSP00000356562.4	Q9UBH6-1
	XPR1	ENST00000367589.3	TSL:1	c.1306+10162A>T		intron	N/A	ENSP00000356561.3	Q9UBH6-2
	XPR1	ENST00000948817.1		c.1501+8491A>T		intron	N/A	ENSP00000618876.1

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51466 AN: 151888 Hom.: 9093 Cov.: 32

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.296

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.325

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

GnomAD4 genome AF: 0.339 AC: 51486 AN: 152006 Hom.: 9098 Cov.: 32 AF XY: 0.339 AC XY: 25188 AN XY: 74292

African (AFR) AF: 0.268 AC: 11112 AN: 41486

American (AMR) AF: 0.345 AC: 5264 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 1180 AN: 3472

East Asian (EAS) AF: 0.161 AC: 834 AN: 5168

South Asian (SAS) AF: 0.337 AC: 1624 AN: 4820

European-Finnish (FIN) AF: 0.415 AC: 4382 AN: 10552

Middle Eastern (MID) AF: 0.301 AC: 88 AN: 292

European-Non Finnish (NFE) AF: 0.382 AC: 25964 AN: 67936

Other (OTH) AF: 0.321 AC: 675 AN: 2106

Alfa AF: 0.218 Hom.: 514

Bravo AF: 0.329

Asia WGS AF: 0.291 AC: 1009 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.2
DANN	Benign	0.39
PhyloP100		1.2
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: rs1533422; hg19: chr1-180814343; COSMIC: COSV62555428;