1-180845207-A-T

Position:

• chr1-180845207-A-T

Variant summary

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

The NM_004736.4(XPR1):​c.1501+8491A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 152,006 control chromosomes in the GnomAD database, including 9,098 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 (9098 hom., cov: 32)
• Consequence: XPR1 NM_004736.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XPR1	NM_004736.4	c.1501+8491A>T		intron_variant		ENST00000367590.9
XPR1	NM_001135669.2	c.1306+10162A>T		intron_variant
XPR1	NR_137330.2	n.1315-18501A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XPR1	ENST00000367590.9	c.1501+8491A>T		intron_variant		1	NM_004736.4	P1
XPR1	ENST00000367589.3	c.1306+10162A>T		intron_variant		1
XPR1	ENST00000498177.1	n.65+8491A>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51466 AN: 151888 Hom.: 9093 Cov.: 32

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.296

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.325

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

GnomAD4 genome AF: 0.339 AC: 51486 AN: 152006 Hom.: 9098 Cov.: 32 AF XY: 0.339 AC XY: 25188 AN XY: 74292

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.345

Gnomad4 ASJ AF: 0.340

Gnomad4 EAS AF: 0.161

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.415

Gnomad4 NFE AF: 0.382

Gnomad4 OTH AF: 0.321

Alfa AF: 0.218 Hom.: 514

Bravo AF: 0.329

Asia WGS AF: 0.291 AC: 1009 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.2
DANN	Benign	0.39

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: rs1533422; hg19: chr1-180814343; COSMIC: COSV62555428;