1-180682478-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_004736.4(XPR1):c.121+67G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0138 in 1,338,454 control chromosomes in the GnomAD database, including 192 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.014 (20 hom., cov: 31)
  • Exomes 𝑓: 0.014 (172 hom.)
• Consequence: XPR1 NM_004736.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.106

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 1-180682478-G-A is Benign according to our data. Variant chr1-180682478-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1211136.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0142 (2163/151852) while in subpopulation AMR AF= 0.0207 (315/15216). AF 95% confidence interval is 0.0188. There are 20 homozygotes in gnomad4. There are 1153 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd at 2163 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XPR1	NM_004736.4	c.121+67G>A		intron_variant		ENST00000367590.9
XPR1	NM_001135669.2	c.121+67G>A		intron_variant
XPR1	NM_001328662.2	c.121+67G>A		intron_variant
XPR1	NR_137330.2	n.301+67G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XPR1	ENST00000367590.9	c.121+67G>A		intron_variant		1	NM_004736.4	P1
XPR1	ENST00000367589.3	c.121+67G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0143 AC: 2163 AN: 151736 Hom.: 20 Cov.: 31

Gnomad AFR AF: 0.00273

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0207

Gnomad ASJ AF: 0.0114

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.0386

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0181

Gnomad OTH AF: 0.0216

GnomAD4 exome AF: 0.0138 AC: 16334 AN: 1186602 Hom.: 172 AF XY: 0.0138 AC XY: 8269 AN XY: 598042

Gnomad4 AFR exome AF: 0.00212

Gnomad4 AMR exome AF: 0.0108

Gnomad4 ASJ exome AF: 0.0153

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00370

Gnomad4 FIN exome AF: 0.0359

Gnomad4 NFE exome AF: 0.0142

Gnomad4 OTH exome AF: 0.0141

GnomAD4 genome AF: 0.0142 AC: 2163 AN: 151852 Hom.: 20 Cov.: 31 AF XY: 0.0155 AC XY: 1153 AN XY: 74242

Gnomad4 AFR AF: 0.00272

Gnomad4 AMR AF: 0.0207

Gnomad4 ASJ AF: 0.0114

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00249

Gnomad4 FIN AF: 0.0386

Gnomad4 NFE AF: 0.0181

Gnomad4 OTH AF: 0.0213

Alfa AF: 0.0186 Hom.: 6

Bravo AF: 0.0128

Asia WGS AF: 0.00173 AC: 6 AN: 3474

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	4.1
Dann	Benign	0.38

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: rs143202929; hg19: chr1-180651614;