Genetic Variant XPR1:c.70-6055C>T (chr1-180676305-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004736.4(XPR1):c.70-6055C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0429 in 152,196 control chromosomes in the GnomAD database, including 492 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 0.043 ( 492 hom., cov: 32)

Consequence

XPR1
NM_004736.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.439

Publications

5 publications found

Variant links:

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

XPR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
XPR1	NM_004736.4 link	c.70-6055C>T	intron_variant	Intron 1 of 14	ENST00000367590.9	NP_004727.2
XPR1	NM_001135669.2 link	c.70-6055C>T	intron_variant	Intron 1 of 13		NP_001129141.1
XPR1	NM_001328662.2 link	c.70-6055C>T	intron_variant	Intron 1 of 10		NP_001315591.1
XPR1	NR_137330.2 link	n.250-6055C>T	intron_variant	Intron 1 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XPR1	ENST00000367590.9 link	c.70-6055C>T		intron_variant	Intron 1 of 14	1	NM_004736.4	ENSP00000356562.4
XPR1	ENST00000367589.3 link	c.70-6055C>T		intron_variant	Intron 1 of 13	1		ENSP00000356561.3

Frequencies

GnomAD3 genomes

AF:

0.0428

AC:

6505

AN:

152082

Hom.:

489

Cov.:

show subpopulations

Gnomad AFR

AF:

0.147

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0209

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000618

Gnomad OTH

AF:

0.0277

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

GnomAD4 genome

AF:

0.0429

AC:

6528

AN:

152196

Hom.:

492

Cov.:

AF XY:

0.0411

AC XY:

3059

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.147

AC:

6103

AN:

41488

American (AMR)

AF:

0.0207

AC:

317

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00104

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000603

AC:

AN:

68002

Other (OTH)

AF:

0.0274

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

281

563

844

1126

1407

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

186

248

310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0170

Hom.:

Bravo

AF:

0.0498

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

5.8

(source)

DANN

Benign

0.73

PhyloP100

0.44

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over