chr1-180787853-A-G
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_004736.4(XPR1):c.222A>G(p.Ser74=) variant causes a splice region, synonymous change. The variant allele was found at a frequency of 0.0000418 in 1,604,740 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000039 ( 0 hom. )
Consequence
XPR1
NM_004736.4 splice_region, synonymous
NM_004736.4 splice_region, synonymous
Scores
2
Splicing: ADA: 0.9468
1
1
Clinical Significance
Conservation
PhyloP100: 3.95
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.23).
BS2
?
High AC in GnomAd at 10 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
XPR1 | NM_004736.4 | c.222A>G | p.Ser74= | splice_region_variant, synonymous_variant | 3/15 | ENST00000367590.9 | |
XPR1 | NM_001135669.2 | c.222A>G | p.Ser74= | splice_region_variant, synonymous_variant | 3/14 | ||
XPR1 | NM_001328662.2 | c.222A>G | p.Ser74= | splice_region_variant, synonymous_variant | 3/11 | ||
XPR1 | NR_137330.2 | n.402A>G | splice_region_variant, non_coding_transcript_exon_variant | 3/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
XPR1 | ENST00000367590.9 | c.222A>G | p.Ser74= | splice_region_variant, synonymous_variant | 3/15 | 1 | NM_004736.4 | P1 | |
XPR1 | ENST00000367589.3 | c.222A>G | p.Ser74= | splice_region_variant, synonymous_variant | 3/14 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000658 AC: 10AN: 152082Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000538 AC: 13AN: 241592Hom.: 0 AF XY: 0.0000767 AC XY: 10AN XY: 130438
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GnomAD4 exome AF: 0.0000392 AC: 57AN: 1452658Hom.: 0 Cov.: 29 AF XY: 0.0000429 AC XY: 31AN XY: 722530
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 23, 2023 | This sequence change affects codon 74 of the XPR1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the XPR1 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs370177151, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with XPR1-related conditions. ClinVar contains an entry for this variant (Variation ID: 2192571). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Name
Calibrated prediction
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at