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GeneBe

11-118893740-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001716.5(CXCR5):c.196G>A(p.Val66Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000849 in 1,614,054 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000080 ( 2 hom. )

Consequence

CXCR5
NM_001716.5 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.393
Variant links:
Genes affected
CXCR5 (HGNC:1060): (C-X-C motif chemokine receptor 5) This gene encodes a multi-pass membrane protein that belongs to the CXC chemokine receptor family. It is expressed in mature B-cells and Burkitt's lymphoma. This cytokine receptor binds to B-lymphocyte chemoattractant (BLC), and is involved in B-cell migration into B-cell follicles of spleen and Peyer patches. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Aug 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.028982818).
BP6
Variant 11-118893740-G-A is Benign according to our data. Variant chr11-118893740-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2299919.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd at 20 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CXCR5NM_001716.5 linkuse as main transcriptc.196G>A p.Val66Met missense_variant 2/2 ENST00000292174.5
CXCR5NM_032966.2 linkuse as main transcriptc.61G>A p.Val21Met missense_variant 1/1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CXCR5ENST00000292174.5 linkuse as main transcriptc.196G>A p.Val66Met missense_variant 2/21 NM_001716.5 P1P32302-1

Frequencies

GnomAD3 genomes
AF:
0.000131
AC:
20
AN:
152178
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000965
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000523
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:
0.000118
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000915
AC:
23
AN:
251282
Hom.:
0
AF XY:
0.000103
AC XY:
14
AN XY:
135822
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.000260
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:
0.000106
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000800
AC:
117
AN:
1461876
Hom.:
2
Cov.:
31
AF XY:
0.0000784
AC XY:
57
AN XY:
727234
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.000291
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000513
Gnomad4 OTH exome
AF:
0.0000993
GnomAD4 genome
AF:
0.000131
AC:
20
AN:
152178
Hom.:
0
Cov.:
32
AF XY:
0.000148
AC XY:
11
AN XY:
74342
show subpopulations
Gnomad4 AFR
AF:
0.0000965
Gnomad4 AMR
AF:
0.000523
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000118
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000132
Hom.:
0
Bravo
AF:
0.000257
ExAC
AF:
0.0000906
AC:
11
EpiCase
AF:
0.000218
EpiControl
AF:
0.000296

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsOct 06, 2021This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.50
T
BayesDel_noAF
Benign
-0.66
Cadd
Benign
1.4
Dann
Benign
0.88
DEOGEN2
Benign
0.15
T
Eigen
Benign
-0.82
Eigen_PC
Benign
-0.78
FATHMM_MKL
Benign
0.043
N
LIST_S2
Benign
0.69
T
M_CAP
Benign
0.0043
T
MetaRNN
Benign
0.029
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-0.14
N
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.29
T
PROVEAN
Benign
0.040
N
REVEL
Benign
0.021
Sift
Benign
0.41
T
Sift4G
Benign
0.30
T
Polyphen
0.041
B
Vest4
0.093
MVP
0.30
MPC
0.77
ClinPred
0.013
T
GERP RS
0.051
Varity_R
0.025
gMVP
0.23

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.

Other links and lift over

dbSNP: rs774152337; hg19: chr11-118764449; API