1-180787871-C-CT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_004736.4(XPR1):c.223+27dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0407 in 1,310,822 control chromosomes in the GnomAD database, including 272 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.039 (132 hom., cov: 31)
  • Exomes 𝑓: 0.041 (140 hom.)
• Consequence: XPR1 NM_004736.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.308

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 1-180787871-C-CT is Benign according to our data. Variant chr1-180787871-C-CT is described in ClinVar as [Benign]. Clinvar id is 1246013.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XPR1	NM_004736.4	c.223+27dup		intron_variant		ENST00000367590.9
XPR1	NM_001135669.2	c.223+27dup		intron_variant
XPR1	NM_001328662.2	c.223+27dup		intron_variant
XPR1	NR_137330.2	n.403+27dup		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XPR1	ENST00000367590.9	c.223+27dup		intron_variant		1	NM_004736.4	P1
XPR1	ENST00000367589.3	c.223+27dup		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0389 AC: 5760 AN: 148172 Hom.: 131 Cov.: 31

Gnomad AFR AF: 0.0625

Gnomad AMI AF: 0.0363

Gnomad AMR AF: 0.0322

Gnomad ASJ AF: 0.0261

Gnomad EAS AF: 0.0104

Gnomad SAS AF: 0.0176

Gnomad FIN AF: 0.0298

Gnomad MID AF: 0.0227

Gnomad NFE AF: 0.0317

Gnomad OTH AF: 0.0413

GnomAD4 exome AF: 0.0409 AC: 47567 AN: 1162564 Hom.: 140 Cov.: 22 AF XY: 0.0409 AC XY: 23540 AN XY: 575694

Gnomad4 AFR exome AF: 0.0727

Gnomad4 AMR exome AF: 0.0336

Gnomad4 ASJ exome AF: 0.0432

Gnomad4 EAS exome AF: 0.0161

Gnomad4 SAS exome AF: 0.0324

Gnomad4 FIN exome AF: 0.0357

Gnomad4 NFE exome AF: 0.0417

Gnomad4 OTH exome AF: 0.0436

GnomAD4 genome AF: 0.0389 AC: 5765 AN: 148258 Hom.: 132 Cov.: 31 AF XY: 0.0383 AC XY: 2771 AN XY: 72336

Gnomad4 AFR AF: 0.0624

Gnomad4 AMR AF: 0.0322

Gnomad4 ASJ AF: 0.0261

Gnomad4 EAS AF: 0.0104

Gnomad4 SAS AF: 0.0177

Gnomad4 FIN AF: 0.0298

Gnomad4 NFE AF: 0.0317

Gnomad4 OTH AF: 0.0410

Bravo AF: 0.0395

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 30, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 03, 2020	- -

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs372311507; hg19: chr1-180757007;