1-180632070-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_004736.4(XPR1):c.-132G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00682 in 1,048,498 control chromosomes in the GnomAD database, including 291 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.027 (188 hom., cov: 32)
  • Exomes 𝑓: 0.0033 (103 hom.)
• Consequence: XPR1 NM_004736.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.22

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=-0.29).
• BP6: Variant 1-180632070-G-A is Benign according to our data. Variant chr1-180632070-G-A is described in ClinVar as [Benign]. Clinvar id is 1258663.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0905 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XPR1	NM_004736.4	c.-132G>A		5_prime_UTR_variant	1/15	ENST00000367590.9
XPR1	NM_001135669.2	c.-132G>A		5_prime_UTR_variant	1/14
XPR1	NM_001328662.2	c.-132G>A		5_prime_UTR_variant	1/11
XPR1	NR_137330.2	n.49G>A		non_coding_transcript_exon_variant	1/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XPR1	ENST00000367590.9	c.-132G>A		5_prime_UTR_variant	1/15	1	NM_004736.4	P1
XPR1	ENST00000367589.3	c.-132G>A		5_prime_UTR_variant	1/14	1

Frequencies

GnomAD3 genomes AF: 0.0274 AC: 4165 AN: 152092 Hom.: 189 Cov.: 32

Gnomad AFR AF: 0.0931

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0143

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000623

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000647

Gnomad OTH AF: 0.0210

GnomAD4 exome AF: 0.00333 AC: 2983 AN: 896288 Hom.: 103 Cov.: 12 AF XY: 0.00282 AC XY: 1299 AN XY: 460830

Gnomad4 AFR exome AF: 0.0923

Gnomad4 AMR exome AF: 0.00812

Gnomad4 ASJ exome AF: 0.000277

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000291

Gnomad4 FIN exome AF: 0.0000637

Gnomad4 NFE exome AF: 0.000533

Gnomad4 OTH exome AF: 0.00728

GnomAD4 genome AF: 0.0274 AC: 4168 AN: 152210 Hom.: 188 Cov.: 32 AF XY: 0.0259 AC XY: 1931 AN XY: 74424

Gnomad4 AFR AF: 0.0929

Gnomad4 AMR AF: 0.0142

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000647

Gnomad4 OTH AF: 0.0208

Alfa AF: 0.00419 Hom.: 1

Bravo AF: 0.0308

Asia WGS AF: 0.00606 AC: 21 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
Cadd	Benign	21
Dann	Uncertain	0.98
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1

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: rs116042397; hg19: chr1-180601206;