Genetic Variant CXCR5:c.*228A>G (chr11-118894891-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001716.5(CXCR5):c.*228A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 454,224 control chromosomes in the GnomAD database, including 44,753 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.48 ( 18682 hom., cov: 32)

Exomes 𝑓: 0.41 ( 26071 hom. )

Consequence

CXCR5
NM_001716.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.31

Publications

44 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCR5	NM_001716.5 link	c.*228A>G		3_prime_UTR_variant	Exon 2 of 2	ENST00000292174.5	NP_001707.1	P32302-1A0N0R2Q2YD84A8K647
CXCR5	NM_032966.2 link	c.*228A>G		3_prime_UTR_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.*228A>G		3_prime_UTR_variant	Exon 2 of 2	1	NM_001716.5	ENSP00000292174.4		P32302-1
BCL9L	ENST00000334801.7 link	c.*3524T>C		3_prime_UTR_variant	Exon 8 of 8	1		ENSP00000335320.3		Q86UU0-1

Frequencies

GnomAD3 genomes

AF:

0.483

AC:

73290

AN:

151886

Hom.:

18632

Cov.:

show subpopulations

Gnomad AFR

AF:

0.636

Gnomad AMI

AF:

0.364

Gnomad AMR

AF:

0.546

Gnomad ASJ

AF:

0.442

Gnomad EAS

AF:

0.303

Gnomad SAS

AF:

0.252

Gnomad FIN

AF:

0.436

Gnomad MID

AF:

0.443

Gnomad NFE

AF:

0.416

Gnomad OTH

AF:

0.472

GnomAD4 exome

AF:

0.405

AC:

122544

AN:

302220

Hom.:

26071

Cov.:

AF XY:

0.404

AC XY:

61932

AN XY:

153134

show subpopulations

African (AFR)

AF:

0.624

AC:

5378

AN:

8624

American (AMR)

AF:

0.560

AC:

6075

AN:

10844

Ashkenazi Jewish (ASJ)

AF:

0.439

AC:

4353

AN:

9910

East Asian (EAS)

AF:

0.225

AC:

5689

AN:

25238

South Asian (SAS)

AF:

0.251

AC:

1955

AN:

7800

European-Finnish (FIN)

AF:

0.424

AC:

15234

AN:

35920

Middle Eastern (MID)

AF:

0.457

AC:

635

AN:

1390

European-Non Finnish (NFE)

AF:

0.408

AC:

75183

AN:

184292

Other (OTH)

AF:

0.442

AC:

8042

AN:

18202

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

3339

6679

10018

13358

16697

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

518

1036

1554

2072

2590

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.483

AC:

73386

AN:

152004

Hom.:

18682

Cov.:

AF XY:

0.482

AC XY:

35771

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.636

AC:

26381

AN:

41460

American (AMR)

AF:

0.547

AC:

8363

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.442

AC:

1533

AN:

3468

East Asian (EAS)

AF:

0.303

AC:

1562

AN:

5158

South Asian (SAS)

AF:

0.253

AC:

1219

AN:

4824

European-Finnish (FIN)

AF:

0.436

AC:

4604

AN:

10570

Middle Eastern (MID)

AF:

0.432

AC:

127

AN:

294

European-Non Finnish (NFE)

AF:

0.416

AC:

28275

AN:

67922

Other (OTH)

AF:

0.468

AC:

990

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1862

3724

5586

7448

9310

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

650

1300

1950

2600

3250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.436

Hom.:

68128

Bravo

AF:

0.501

Asia WGS

AF:

0.288

AC:

1000

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.027

(source)

DANN

Benign

0.24

PhyloP100

-1.3

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over