1-180788492-T-C

Position:

• chr1-180788492-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004736.4(XPR1):​c.223+638T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 151,960 control chromosomes in the GnomAD database, including 9,181 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 0.34 (9181 hom., cov: 31)
• Consequence: XPR1 NM_004736.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.477

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XPR1	NM_004736.4	c.223+638T>C		intron_variant		ENST00000367590.9	NP_004727.2
XPR1	NM_001135669.2	c.223+638T>C		intron_variant			NP_001129141.1
XPR1	NM_001328662.2	c.223+638T>C		intron_variant			NP_001315591.1
XPR1	NR_137330.2	n.403+638T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XPR1	ENST00000367590.9	c.223+638T>C		intron_variant		1	NM_004736.4	ENSP00000356562.4
XPR1	ENST00000367589.3	c.223+638T>C		intron_variant		1		ENSP00000356561.3

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51770 AN: 151842 Hom.: 9175 Cov.: 31

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.329

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.341 AC: 51799 AN: 151960 Hom.: 9181 Cov.: 31 AF XY: 0.341 AC XY: 25309 AN XY: 74262

Gnomad4 AFR AF: 0.272

Gnomad4 AMR AF: 0.347

Gnomad4 ASJ AF: 0.341

Gnomad4 EAS AF: 0.174

Gnomad4 SAS AF: 0.340

Gnomad4 FIN AF: 0.413

Gnomad4 NFE AF: 0.383

Gnomad4 OTH AF: 0.325

Alfa AF: 0.355 Hom.: 1995

Bravo AF: 0.332

Asia WGS AF: 0.300 AC: 1042 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	14
DANN	Benign	0.77

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: rs7544774; hg19: chr1-180757628;