1-180879945-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004736.4(XPR1):c.1809-131A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 930,118 control chromosomes in the GnomAD database, including 6,522 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1239 hom., cov: 32)
  • Exomes 𝑓: 0.11 (5283 hom.)
• Consequence: XPR1 NM_004736.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.146

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 1-180879945-A-G is Benign according to our data. Variant chr1-180879945-A-G is described in ClinVar as [Benign]. Clinvar id is 1290105.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XPR1	NM_004736.4	c.1809-131A>G		intron_variant		ENST00000367590.9
XPR1	NM_001135669.2	c.1614-131A>G		intron_variant
XPR1	NR_137330.2	n.1622-131A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XPR1	ENST00000367590.9	c.1809-131A>G		intron_variant		1	NM_004736.4	P1
XPR1	ENST00000367589.3	c.1614-131A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 17951 AN: 151426 Hom.: 1236 Cov.: 32

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.0507

Gnomad AMR AF: 0.0938

Gnomad ASJ AF: 0.0949

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.0787

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0935

Gnomad OTH AF: 0.104

GnomAD4 exome AF: 0.105 AC: 81791 AN: 778574 Hom.: 5283 AF XY: 0.104 AC XY: 41131 AN XY: 397246

Gnomad4 AFR exome AF: 0.150

Gnomad4 AMR exome AF: 0.0852

Gnomad4 ASJ exome AF: 0.0915

Gnomad4 EAS exome AF: 0.302

Gnomad4 SAS exome AF: 0.0743

Gnomad4 FIN exome AF: 0.108

Gnomad4 NFE exome AF: 0.0953

Gnomad4 OTH exome AF: 0.107

GnomAD4 genome AF: 0.119 AC: 17967 AN: 151544 Hom.: 1239 Cov.: 32 AF XY: 0.119 AC XY: 8788 AN XY: 74032

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.0940

Gnomad4 ASJ AF: 0.0949

Gnomad4 EAS AF: 0.326

Gnomad4 SAS AF: 0.0784

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.0935

Gnomad4 OTH AF: 0.103

Alfa AF: 0.0919 Hom.: 953

Bravo AF: 0.119

Asia WGS AF: 0.151 AC: 526 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 17, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.1
Dann	Benign	0.57

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: rs2271668; hg19: chr1-180849081; COSMIC: COSV62557444; COSMIC: COSV62557444;