rs778895457

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001024644.2(XCR1):c.398G>A(p.Ser133Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,610,488 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

XCR1
NM_001024644.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.440

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]

XCR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07080534).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XCR1	NM_001024644.2 link	c.398G>A	p.Ser133Asn	missense_variant	Exon 2 of 2	ENST00000309285.4	NP_001019815.1	P46094Q689E2Q502V0
XCR1	NM_001381860.1 link	c.398G>A	p.Ser133Asn	missense_variant	Exon 4 of 4		NP_001368789.1
XCR1	NM_005283.3 link	c.398G>A	p.Ser133Asn	missense_variant	Exon 3 of 3		NP_005274.1	P46094Q689E2Q502V0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
XCR1	ENST00000309285.4 link	c.398G>A	p.Ser133Asn	missense_variant	Exon 2 of 2	1	NM_001024644.2	ENSP00000310405.3	P46094
XCR1	ENST00000395946.3 link	c.398G>A	p.Ser133Asn	missense_variant	Exon 3 of 3	1		ENSP00000379277.3	P46094Q689E2
XCR1	ENST00000683768.1 link	c.398G>A	p.Ser133Asn	missense_variant	Exon 6 of 6			ENSP00000507745.1	P46094

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000413

AC:

AN:

242386

Hom.:

AF XY:

0.00

AC XY:

AN XY:

130970

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000919

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1458412

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725216

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.01e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152076

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000413

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 29, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.398G>A (p.S133N) alteration is located in exon 3 (coding exon 1) of the XCR1 gene. This alteration results from a G to A substitution at nucleotide position 398, causing the serine (S) at amino acid position 133 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.73

CADD

Benign

5.6

DANN

Benign

0.74

DEOGEN2

Benign

0.054

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.57

M_CAP

Benign

0.0084

MetaRNN

Benign

0.071

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.28

PrimateAI

Benign

0.24

PROVEAN

Benign

1.6

REVEL

Benign

0.064

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0010

Vest4

0.044

MutPred

0.58

Gain of helix (P = 0.132);

MVP

0.23

MPC

0.33

ClinPred

0.025

GERP RS

2.4

Varity_R

0.049

gMVP

0.090

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over