chr1-180676305-C-T

Variant names:

• chr1-180676305-C-T
• rs7527074
• NM_004736.4:c.70-6055C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.439
• Publications: 5 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: Genomics England PanelApp, Illumina, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• bilateral striopallidodentate calcinosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004736.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XPR1	NM_004736.4	MANE Select	c.70-6055C>T		intron	N/A	NP_004727.2
	XPR1	NM_001135669.2		c.70-6055C>T		intron	N/A	NP_001129141.1	Q9UBH6-2
	XPR1	NM_001328662.2		c.70-6055C>T		intron	N/A	NP_001315591.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XPR1	ENST00000367590.9	TSL:1 MANE Select	c.70-6055C>T		intron	N/A	ENSP00000356562.4	Q9UBH6-1
	XPR1	ENST00000367589.3	TSL:1	c.70-6055C>T		intron	N/A	ENSP00000356561.3	Q9UBH6-2
	XPR1	ENST00000948817.1		c.70-6055C>T		intron	N/A	ENSP00000618876.1

Frequencies

GnomAD3 genomes AF: 0.0428 AC: 6505 AN: 152082 Hom.: 489 Cov.: 32

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.: 32 AF XY: 0.0411 AC XY: 3059 AN XY: 74432

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: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000603 AC: 41 AN: 68002

Other (OTH) AF: 0.0274 AC: 58 AN: 2116

Alfa AF: 0.0170 Hom.: 28

Bravo AF: 0.0498

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.8
DANN	Benign	0.73
PhyloP100		0.44
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: rs7527074; hg19: chr1-180645441;