1-180787920-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004736.4(XPR1):c.223+66A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 1,197,858 control chromosomes in the GnomAD database, including 84,086 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.32 (8274 hom., cov: 31)
  • Exomes 𝑓: 0.38 (75812 hom.)
• Consequence: XPR1 NM_004736.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.17

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=-0.81).
• BP6: Variant 1-180787920-A-G is Benign according to our data. Variant chr1-180787920-A-G is described in ClinVar as [Benign]. Clinvar id is 1281131.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XPR1	NM_004736.4	c.223+66A>G		intron_variant		ENST00000367590.9
XPR1	NM_001135669.2	c.223+66A>G		intron_variant
XPR1	NM_001328662.2	c.223+66A>G		intron_variant
XPR1	NR_137330.2	n.403+66A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XPR1	ENST00000367590.9	c.223+66A>G		intron_variant		1	NM_004736.4	P1
XPR1	ENST00000367589.3	c.223+66A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47898 AN: 151688 Hom.: 8270 Cov.: 31

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.305

GnomAD4 exome AF: 0.375 AC: 392766 AN: 1046052 Hom.: 75812 AF XY: 0.374 AC XY: 199499 AN XY: 533656

Gnomad4 AFR exome AF: 0.178

Gnomad4 AMR exome AF: 0.308

Gnomad4 ASJ exome AF: 0.336

Gnomad4 EAS exome AF: 0.215

Gnomad4 SAS exome AF: 0.346

Gnomad4 FIN exome AF: 0.420

Gnomad4 NFE exome AF: 0.395

Gnomad4 OTH exome AF: 0.355

GnomAD4 genome AF: 0.316 AC: 47909 AN: 151806 Hom.: 8274 Cov.: 31 AF XY: 0.317 AC XY: 23499 AN XY: 74160

Gnomad4 AFR AF: 0.184

Gnomad4 AMR AF: 0.335

Gnomad4 ASJ AF: 0.342

Gnomad4 EAS AF: 0.174

Gnomad4 SAS AF: 0.340

Gnomad4 FIN AF: 0.414

Gnomad4 NFE AF: 0.383

Gnomad4 OTH AF: 0.301

Alfa AF: 0.366 Hom.: 10292

Bravo AF: 0.303

Asia WGS AF: 0.289 AC: 1004 AN: 3476

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 30, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	9.5
Dann	Benign	0.73

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: rs3761904; hg19: chr1-180757056; COSMIC: COSV62560383;