1-180787871-C-CTT

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_004736.4(XPR1):c.223+26_223+27dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000784 in 1,352,446 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0033 (4 hom., cov: 31)
  • Exomes 𝑓: 0.00048 (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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 1-180787871-C-CTT is Benign according to our data. Variant chr1-180787871-C-CTT is described in ClinVar as [Benign]. Clinvar id is 1599735.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 483 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XPR1	NM_004736.4	c.223+26_223+27dup		intron_variant		ENST00000367590.9
XPR1	NM_001135669.2	c.223+26_223+27dup		intron_variant
XPR1	NM_001328662.2	c.223+26_223+27dup		intron_variant
XPR1	NR_137330.2	n.403+26_403+27dup		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XPR1	ENST00000367590.9	c.223+26_223+27dup		intron_variant		1	NM_004736.4	P1
XPR1	ENST00000367589.3	c.223+26_223+27dup		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.00326 AC: 483 AN: 148224 Hom.: 4 Cov.: 31

Gnomad AFR AF: 0.0110

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00175

Gnomad ASJ AF: 0.000293

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000212

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000450

Gnomad OTH AF: 0.00295

GnomAD4 exome AF: 0.000475 AC: 572 AN: 1204136 Hom.: 0 Cov.: 22 AF XY: 0.000447 AC XY: 267 AN XY: 597330

Gnomad4 AFR exome AF: 0.00952

Gnomad4 AMR exome AF: 0.000777

Gnomad4 ASJ exome AF: 0.000692

Gnomad4 EAS exome AF: 0.0000327

Gnomad4 SAS exome AF: 0.0000925

Gnomad4 FIN exome AF: 0.0000449

Gnomad4 NFE exome AF: 0.000234

Gnomad4 OTH exome AF: 0.00106

GnomAD4 genome AF: 0.00329 AC: 488 AN: 148310 Hom.: 4 Cov.: 31 AF XY: 0.00357 AC XY: 258 AN XY: 72364

Gnomad4 AFR AF: 0.0111

Gnomad4 AMR AF: 0.00175

Gnomad4 ASJ AF: 0.000293

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000213

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000450

Gnomad4 OTH AF: 0.00293

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

Jan 11, 2024

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Computational scores

Source: dbNSFP v4.3

Splicing

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;