1-180879945-A-G

Variant names:

• chr1-180879945-A-G
• rs2271668
• NM_004736.4:c.1809-131A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.146
• Publications: 6 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

ENSG00000294697 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1290105.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
XPR1	NM_004736.4	c.1809-131A>G		intron_variant	Intron 13 of 14	ENST00000367590.9	NP_004727.2
XPR1	NM_001135669.2	c.1614-131A>G		intron_variant	Intron 12 of 13		NP_001129141.1
XPR1	NR_137330.2	n.1622-131A>G		intron_variant	Intron 11 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XPR1	ENST00000367590.9	c.1809-131A>G		intron_variant	Intron 13 of 14	1	NM_004736.4	ENSP00000356562.4
XPR1	ENST00000367589.3	c.1614-131A>G		intron_variant	Intron 12 of 13	1		ENSP00000356561.3
ENSG00000294697	ENST00000725271.1	n.649-19145T>C		intron_variant	Intron 1 of 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

African (AFR) AF: 0.150 AC: 2866 AN: 19044

American (AMR) AF: 0.0852 AC: 2076 AN: 24374

Ashkenazi Jewish (ASJ) AF: 0.0915 AC: 1516 AN: 16560

East Asian (EAS) AF: 0.302 AC: 10307 AN: 34152

South Asian (SAS) AF: 0.0743 AC: 4022 AN: 54130

European-Finnish (FIN) AF: 0.108 AC: 4688 AN: 43222

Middle Eastern (MID) AF: 0.0805 AC: 338 AN: 4200

European-Non Finnish (NFE) AF: 0.0953 AC: 52028 AN: 546078

Other (OTH) AF: 0.107 AC: 3950 AN: 36814

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

African (AFR) AF: 0.153 AC: 6332 AN: 41260

American (AMR) AF: 0.0940 AC: 1434 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.0949 AC: 328 AN: 3458

East Asian (EAS) AF: 0.326 AC: 1676 AN: 5144

South Asian (SAS) AF: 0.0784 AC: 375 AN: 4784

European-Finnish (FIN) AF: 0.114 AC: 1195 AN: 10484

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0935 AC: 6345 AN: 67860

Other (OTH) AF: 0.103 AC: 216 AN: 2104

Alfa AF: 0.0940 Hom.: 1263

Bravo AF: 0.119

Asia WGS AF: 0.151 AC: 526 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 17, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.57
PhyloP100		-0.15
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: rs2271668; hg19: chr1-180849081; COSMIC: COSV62557444; COSMIC: COSV62557444;