rs2271668

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-180879945-A-C
• chr1-180879945-A-G
• chr1-180879945-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004736.4(XPR1):​c.1809-131A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: XPR1 NM_004736.4 intron
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XPR1	NM_004736.4	c.1809-131A>C		intron_variant	Intron 13 of 14	ENST00000367590.9	NP_004727.2
XPR1	NM_001135669.2	c.1614-131A>C		intron_variant	Intron 12 of 13		NP_001129141.1
XPR1	NR_137330.2	n.1622-131A>C		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>C		intron_variant	Intron 13 of 14	1	NM_004736.4	ENSP00000356562.4
XPR1	ENST00000367589.3	c.1614-131A>C		intron_variant	Intron 12 of 13	1		ENSP00000356561.3
ENSG00000294697	ENST00000725271.1	n.649-19145T>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 779120 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 397550

African (AFR) AF: 0.00 AC: 0 AN: 19046

American (AMR) AF: 0.00 AC: 0 AN: 24378

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16560

East Asian (EAS) AF: 0.00 AC: 0 AN: 34170

South Asian (SAS) AF: 0.00 AC: 0 AN: 54140

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43264

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4204

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 546522

Other (OTH) AF: 0.00 AC: 0 AN: 36836

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1263

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.64
PhyloP100		-0.15

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;