1-180763987-T-G

Position:

• chr1-180763987-T-G

Variant summary

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

The NM_004736.4(XPR1):​c.122-23766T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.765 in 152,172 control chromosomes in the GnomAD database, including 44,699 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 0.76 (44699 hom., cov: 33)
• Consequence: XPR1 NM_004736.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.79

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.815 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XPR1	NM_004736.4	c.122-23766T>G		intron_variant		ENST00000367590.9	NP_004727.2
XPR1	NM_001135669.2	c.122-23766T>G		intron_variant			NP_001129141.1
XPR1	NM_001328662.2	c.122-23766T>G		intron_variant			NP_001315591.1
XPR1	NR_137330.2	n.302-23766T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XPR1	ENST00000367590.9	c.122-23766T>G		intron_variant		1	NM_004736.4	ENSP00000356562	P1
XPR1	ENST00000367589.3	c.122-23766T>G		intron_variant		1		ENSP00000356561

Frequencies

GnomAD3 genomes AF: 0.765 AC: 116250 AN: 152054 Hom.: 44659 Cov.: 33

Gnomad AFR AF: 0.822

Gnomad AMI AF: 0.655

Gnomad AMR AF: 0.764

Gnomad ASJ AF: 0.692

Gnomad EAS AF: 0.818

Gnomad SAS AF: 0.703

Gnomad FIN AF: 0.788

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.733

Gnomad OTH AF: 0.718

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

GnomAD4 genome AF: 0.765 AC: 116348 AN: 152172 Hom.: 44699 Cov.: 33 AF XY: 0.766 AC XY: 57004 AN XY: 74382

Gnomad4 AFR AF: 0.822

Gnomad4 AMR AF: 0.764

Gnomad4 ASJ AF: 0.692

Gnomad4 EAS AF: 0.818

Gnomad4 SAS AF: 0.703

Gnomad4 FIN AF: 0.788

Gnomad4 NFE AF: 0.733

Gnomad4 OTH AF: 0.715

Alfa AF: 0.737 Hom.: 23656

Bravo AF: 0.766

Asia WGS AF: 0.744 AC: 2584 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.55
DANN	Benign	0.68

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: rs2331886; hg19: chr1-180733123;