rs140843011

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001716.5(CXCR5):c.1004G>A(p.Arg335Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000109 in 1,568,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

CXCR5
NM_001716.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.21

Publications

1 publications found

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]

CXCR5 links:

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]

BCL9L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.061409354).

BS2

High AC in GnomAd4 at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCR5	NM_001716.5 link	c.1004G>A	p.Arg335Gln	missense_variant	Exon 2 of 2	ENST00000292174.5	NP_001707.1	P32302-1A0N0R2Q2YD84A8K647
CXCR5	NM_032966.2 link	c.869G>A	p.Arg290Gln	missense_variant	Exon 1 of 1		NP_116743.1	P32302-2Q2YD84

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCR5	ENST00000292174.5 link	c.1004G>A	p.Arg335Gln	missense_variant	Exon 2 of 2	1	NM_001716.5	ENSP00000292174.4		P32302-1
BCL9L	ENST00000334801.7 link	c.*3867C>T		3_prime_UTR_variant	Exon 8 of 8	1		ENSP00000335320.3		Q86UU0-1

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.000103

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000145

AC:

AN:

213382

AF XY:

0.000106

show subpopulations

Gnomad AFR exome

AF:

0.000440

Gnomad AMR exome

AF:

0.000190

Gnomad ASJ exome

AF:

0.000159

Gnomad EAS exome

AF:

0.0000554

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000134

Gnomad OTH exome

AF:

0.000389

GnomAD4 exome

AF:

0.000111

AC:

157

AN:

1415780

Hom.:

Cov.:

AF XY:

0.000109

AC XY:

AN XY:

698132

show subpopulations

African (AFR)

AF:

0.000122

AC:

AN:

32782

American (AMR)

AF:

0.000190

AC:

AN:

42090

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22840

East Asian (EAS)

AF:

0.000102

AC:

AN:

39286

South Asian (SAS)

AF:

0.000128

AC:

AN:

78230

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49822

Middle Eastern (MID)

AF:

0.00378

AC:

AN:

5558

European-Non Finnish (NFE)

AF:

0.0000883

AC:

AN:

1086710

Other (OTH)

AF:

0.000239

AC:

AN:

58462

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000919

AC:

AN:

152308

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.000144

AC:

AN:

41556

American (AMR)

AF:

0.0000654

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.532

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000171

Hom.:

Bravo

AF:

0.000125

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000157

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 11, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1004G>A (p.R335Q) 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 1004, causing the arginine (R) at amino acid position 335 to be replaced by a glutamine (Q). 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

0.097

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.51

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.076

Eigen

Benign

-0.076

Eigen_PC

Benign

0.0065

FATHMM_MKL

Benign

0.66

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.018

MetaRNN

Benign

0.061

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.095

PhyloP100

3.2

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.36

REVEL

Benign

0.052

Sift

Benign

0.27

Sift4G

Benign

0.34

Polyphen

0.73

Vest4

0.093

MVP

0.57

MPC

1.2

ClinPred

0.011

GERP RS

3.2

Varity_R

0.082

gMVP

0.40

Mutation Taster

=91/9

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs140843011

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over