1-180787871-CT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_004736.4(XPR1):c.223+27del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0129 in 1,273,844 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 31)
  • Exomes 𝑓: 0.015 (0 hom.)
• Consequence: XPR1 NM_004736.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.308

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 -10 ACMG points.

• BP6: Variant 1-180787871-CT-C is Benign according to our data. Variant chr1-180787871-CT-C is described in ClinVar as [Benign]. Clinvar id is 1987577.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-180787871-CT-C is described in Lovd as [Benign]. Variant chr1-180787871-CT-C is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0146 (16448/1125764) while in subpopulation AMR AF= 0.0281 (815/28972). AF 95% confidence interval is 0.0265. There are 0 homozygotes in gnomad4_exome. There are 8238 alleles in male gnomad4_exome subpopulation. Median coverage is 22. This position pass quality control queck.
• BS2: High AC in GnomAd at 16 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XPR1	NM_004736.4	c.223+27del		intron_variant		ENST00000367590.9
XPR1	NM_001135669.2	c.223+27del		intron_variant
XPR1	NM_001328662.2	c.223+27del		intron_variant
XPR1	NR_137330.2	n.403+27del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XPR1	ENST00000367590.9	c.223+27del		intron_variant		1	NM_004736.4	P1
XPR1	ENST00000367589.3	c.223+27del		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.000108 AC: 16 AN: 148080 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000148

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000135

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000518

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000450

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0146 AC: 16448 AN: 1125764 Hom.: 0 Cov.: 22 AF XY: 0.0148 AC XY: 8238 AN XY: 555728

Gnomad4 AFR exome AF: 0.0129

Gnomad4 AMR exome AF: 0.0281

Gnomad4 ASJ exome AF: 0.0207

Gnomad4 EAS exome AF: 0.0147

Gnomad4 SAS exome AF: 0.0231

Gnomad4 FIN exome AF: 0.00999

Gnomad4 NFE exome AF: 0.0137

Gnomad4 OTH exome AF: 0.0161

GnomAD4 genome AF: 0.000108 AC: 16 AN: 148080 Hom.: 0 Cov.: 31 AF XY: 0.000152 AC XY: 11 AN XY: 72192

Gnomad4 AFR AF: 0.000148

Gnomad4 AMR AF: 0.000135

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000518

Gnomad4 NFE AF: 0.0000450

Gnomad4 OTH AF: 0.00

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

Invitae

Feb 08, 2022

- -

Computational scores

Source: dbNSFP v4.3

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: rs372311507; hg19: chr1-180757007;