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GeneBe

11-118894004-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_001716.5(CXCR5):c.460G>A(p.Ala154Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,474 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000062 ( 1 hom. )

Consequence

CXCR5
NM_001716.5 missense

Scores

3
11
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.67
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 Uncertain_significance. Variant got 2 ACMG points.

PP3
MetaRNN computational evidence supports a deleterious effect, 0.888

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CXCR5NM_001716.5 linkuse as main transcriptc.460G>A p.Ala154Thr missense_variant 2/2 ENST00000292174.5
CXCR5NM_032966.2 linkuse as main transcriptc.325G>A p.Ala109Thr missense_variant 1/1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CXCR5ENST00000292174.5 linkuse as main transcriptc.460G>A p.Ala154Thr missense_variant 2/21 NM_001716.5 P1P32302-1
BCL9LENST00000334801.7 linkuse as main transcriptc.*4411C>T 3_prime_UTR_variant 8/81 P4Q86UU0-1

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
152022
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
250908
Hom.:
1
AF XY:
0.0000221
AC XY:
3
AN XY:
135722
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:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000616
AC:
9
AN:
1461452
Hom.:
1
Cov.:
31
AF XY:
0.00000963
AC XY:
7
AN XY:
727060
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:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.0000662
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
152022
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74232
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

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 GeneticsDec 15, 2022The c.460G>A (p.A154T) 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 460, causing the alanine (A) at amino acid position 154 to be replaced by a threonine (T). 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
Uncertain
0.46
BayesDel_addAF
Uncertain
0.027
T
BayesDel_noAF
Benign
-0.10
Cadd
Uncertain
25
Dann
Uncertain
1.0
DEOGEN2
Uncertain
0.46
T
Eigen
Uncertain
0.49
Eigen_PC
Uncertain
0.35
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.83
T
M_CAP
Uncertain
0.16
D
MetaRNN
Pathogenic
0.89
D
MetaSVM
Benign
-0.56
T
MutationAssessor
Benign
1.9
L
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.74
T
PROVEAN
Uncertain
-3.9
D
REVEL
Uncertain
0.56
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.61
MutPred
0.72
Gain of glycosylation at A154 (P = 0.0255);
MVP
0.68
MPC
1.8
ClinPred
0.99
D
GERP RS
4.0
Varity_R
0.80
gMVP
0.61

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: rs373196739; hg19: chr11-118764713; API