GeneBe

rs1708144736

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001024644.2(XCR1):​c.506A>C​(p.Lys169Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

XCR1
NM_001024644.2 missense

Scores

18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.80

Publications

0 publications found
Variant links:
Genes affected
XCR1 (HGNC:1625): (X-C motif chemokine receptor 1) The protein encoded by this gene is a chemokine receptor belonging to the G protein-coupled receptor superfamily. The family members are characterized by the presence of 7 transmembrane domains. The encoded protein transduces a signal by increasing the intracellular calcium ion level. The viral macrophage inflammatory protein-II is an antagonist of this receptor and blocks signaling. Some studies have implicated a cluster of genes at 3p21.31, including this gene, as associated with COVID-19 risk. The encoded protein may also play a role in cell proliferation and migration in several types of cancer. [provided by RefSeq, Jan 2023]

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.09088504).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001024644.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
XCR1
NM_001024644.2
MANE Select
c.506A>Cp.Lys169Thr
missense
Exon 2 of 2NP_001019815.1P46094
XCR1
NM_001381860.1
c.506A>Cp.Lys169Thr
missense
Exon 4 of 4NP_001368789.1P46094
XCR1
NM_005283.3
c.506A>Cp.Lys169Thr
missense
Exon 3 of 3NP_005274.1P46094

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
XCR1
ENST00000309285.4
TSL:1 MANE Select
c.506A>Cp.Lys169Thr
missense
Exon 2 of 2ENSP00000310405.3P46094
XCR1
ENST00000395946.3
TSL:1
c.506A>Cp.Lys169Thr
missense
Exon 3 of 3ENSP00000379277.3P46094
XCR1
ENST00000683768.1
c.506A>Cp.Lys169Thr
missense
Exon 6 of 6ENSP00000507745.1P46094

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

ClinVar submissions
Significance:Uncertain significance
Revision:criteria provided, single submitter
View on ClinVar
Pathogenic
VUS
Benign
Condition
-
1
-
not specified (1)

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
3.1
DANN
Benign
0.68
DEOGEN2
Benign
0.10
T
Eigen
Benign
-0.82
Eigen_PC
Benign
-0.77
FATHMM_MKL
Benign
0.26
N
LIST_S2
Benign
0.50
T
M_CAP
Benign
0.036
D
MetaRNN
Benign
0.091
T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
0.51
N
PhyloP100
1.8
PrimateAI
Benign
0.24
T
PROVEAN
Benign
-0.90
N
REVEL
Benign
0.15
Sift
Benign
0.23
T
Sift4G
Benign
0.33
T
Polyphen
0.034
B
Vest4
0.071
MutPred
0.67
Loss of methylation at K169 (P = 0.0126)
MVP
0.58
MPC
0.43
ClinPred
0.23
T
GERP RS
1.5
Varity_R
0.096
gMVP
0.37
Mutation Taster
=92/8
polymorphism

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

Other links and lift over

dbSNP: rs1708144736; hg19: chr3-46062934; API