1-180788008-G-A

Position:

• chr1-180788008-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004736.4(XPR1):​c.223+154G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0426 in 152,096 control chromosomes in the GnomAD database, including 493 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.043 (493 hom., cov: 32)
• Consequence: XPR1 NM_004736.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.125

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 1-180788008-G-A is Benign according to our data. Variant chr1-180788008-G-A is described in ClinVar as [Benign]. Clinvar id is 1280159.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XPR1	NM_004736.4	c.223+154G>A		intron_variant		ENST00000367590.9	NP_004727.2
XPR1	NM_001135669.2	c.223+154G>A		intron_variant			NP_001129141.1
XPR1	NM_001328662.2	c.223+154G>A		intron_variant			NP_001315591.1
XPR1	NR_137330.2	n.403+154G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XPR1	ENST00000367590.9	c.223+154G>A		intron_variant		1	NM_004736.4	ENSP00000356562	P1
XPR1	ENST00000367589.3	c.223+154G>A		intron_variant		1		ENSP00000356561

Frequencies

GnomAD3 genomes AF: 0.0425 AC: 6454 AN: 151978 Hom.: 485 Cov.: 32

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0211

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: 0.0278

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

GnomAD4 genome AF: 0.0426 AC: 6484 AN: 152096 Hom.: 493 Cov.: 32 AF XY: 0.0408 AC XY: 3032 AN XY: 74358

Gnomad4 AFR AF: 0.146

Gnomad4 AMR AF: 0.0210

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000603

Gnomad4 OTH AF: 0.0275

Alfa AF: 0.0339 Hom.: 36

Bravo AF: 0.0495

Asia WGS AF: 0.0120 AC: 41 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.68
DANN	Benign	0.58

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: rs73036576; hg19: chr1-180757144;