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GeneBe

11-118894376-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001716.5(CXCR5):c.832G>A(p.Val278Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000316 in 1,614,150 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

CXCR5
NM_001716.5 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.14
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]
BCL9L (HGNC:23688): (BCL9 like) Enables beta-catenin binding activity. Involved in several processes, including negative regulation of transforming growth factor beta receptor signaling pathway; positive regulation of epithelial to mesenchymal transition; and positive regulation of transcription by RNA polymerase II. Located in nucleolus and nucleoplasm. Part of beta-catenin-TCF complex. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.1117101).
BS2
High AC in GnomAd at 17 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CXCR5NM_001716.5 linkuse as main transcriptc.832G>A p.Val278Ile missense_variant 2/2 ENST00000292174.5
CXCR5NM_032966.2 linkuse as main transcriptc.697G>A p.Val233Ile missense_variant 1/1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CXCR5ENST00000292174.5 linkuse as main transcriptc.832G>A p.Val278Ile missense_variant 2/21 NM_001716.5 P1P32302-1
BCL9LENST00000334801.7 linkuse as main transcriptc.*4039C>T 3_prime_UTR_variant 8/81 P4Q86UU0-1

Frequencies

GnomAD3 genomes
AF:
0.000112
AC:
17
AN:
152174
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000266
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
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:
0.0000441
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000598
AC:
15
AN:
251006
Hom.:
0
AF XY:
0.0000516
AC XY:
7
AN XY:
135698
show subpopulations
Gnomad AFR exome
AF:
0.000431
Gnomad AMR exome
AF:
0.0000289
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:
0.0000618
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000233
AC:
34
AN:
1461858
Hom.:
0
Cov.:
31
AF XY:
0.0000193
AC XY:
14
AN XY:
727232
show subpopulations
Gnomad4 AFR exome
AF:
0.000329
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.000112
AC:
17
AN:
152292
Hom.:
0
Cov.:
32
AF XY:
0.000121
AC XY:
9
AN XY:
74476
show subpopulations
Gnomad4 AFR
AF:
0.000265
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.0000763
Hom.:
0
Bravo
AF:
0.000174
ESP6500AA
AF:
0.000455
AC:
2
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000659
AC:
8
EpiCase
AF:
0.00
EpiControl
AF:
0.000119

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMar 02, 2023The c.832G>A (p.V278I) alteration is located in exon 2 (coding exon 2) of the CXCR5 gene. This alteration results from a G to A substitution at nucleotide position 832, causing the valine (V) at amino acid position 278 to be replaced by an isoleucine (I). 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
0.14
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.37
Cadd
Benign
20
Dann
Uncertain
1.0
DEOGEN2
Benign
0.097
T
Eigen
Benign
0.17
Eigen_PC
Benign
0.086
FATHMM_MKL
Benign
0.64
D
LIST_S2
Benign
0.69
T
M_CAP
Benign
0.048
D
MetaRNN
Benign
0.11
T
MetaSVM
Benign
-0.42
T
MutationAssessor
Benign
1.3
L
MutationTaster
Benign
1.0
D;N
PrimateAI
Benign
0.29
T
PROVEAN
Benign
-0.65
N
REVEL
Benign
0.27
Sift
Uncertain
0.017
D
Sift4G
Uncertain
0.057
T
Polyphen
1.0
D
Vest4
0.076
MVP
0.83
MPC
0.66
ClinPred
0.027
T
GERP RS
2.7
Varity_R
0.051
gMVP
0.28

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: rs145276178; hg19: chr11-118765085; COSMIC: COSV99420369; COSMIC: COSV99420369; API