Genetic Variant CXCR5:p.Thr338Thr (chr11-118894558-G-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001716.5(CXCR5):c.1014G>C(p.Thr338Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 1,561,110 control chromosomes in the GnomAD database, including 64,566 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 0.34 ( 9477 hom., cov: 33)

Exomes 𝑓: 0.27 ( 55089 hom. )

Consequence

CXCR5
NM_001716.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0360

Publications

21 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

new If you want to explore the variant's impact on the transcript NM_001716.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP7

Synonymous conserved (PhyloP=0.036 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001716.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCR5	NM_001716.5	MANE Select	c.1014G>C	p.Thr338Thr	synonymous	Exon 2 of 2	NP_001707.1	P32302-1
	CXCR5	NM_032966.2		c.879G>C	p.Thr293Thr	synonymous	Exon 1 of 1	NP_116743.1	P32302-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCR5	ENST00000292174.5	TSL:1 MANE Select	c.1014G>C	p.Thr338Thr	synonymous	Exon 2 of 2	ENSP00000292174.4	P32302-1
	BCL9L	ENST00000334801.7	TSL:1	c.*3857C>G		3_prime_UTR	Exon 8 of 8	ENSP00000335320.3	Q86UU0-1

Frequencies

GnomAD3 genomes

AF:

0.339

AC:

51503

AN:

152044

Hom.:

9436

Cov.:

show subpopulations

Gnomad AFR

AF:

0.458

Gnomad AMI

AF:

0.259

Gnomad AMR

AF:

0.433

Gnomad ASJ

AF:

0.240

Gnomad EAS

AF:

0.219

Gnomad SAS

AF:

0.164

Gnomad FIN

AF:

0.325

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.276

Gnomad OTH

AF:

0.312

GnomAD2 exomes

AF:

0.309

AC:

65482

AN:

211768

AF XY:

0.295

show subpopulations

Gnomad AFR exome

AF:

0.453

Gnomad AMR exome

AF:

0.504

Gnomad ASJ exome

AF:

0.240

Gnomad EAS exome

AF:

0.229

Gnomad FIN exome

AF:

0.320

Gnomad NFE exome

AF:

0.271

Gnomad OTH exome

AF:

0.278

GnomAD4 exome

AF:

0.272

AC:

382938

AN:

1408948

Hom.:

55089

Cov.:

AF XY:

0.268

AC XY:

185882

AN XY:

693688

show subpopulations

African (AFR)

AF:

0.453

AC:

14759

AN:

32558

American (AMR)

AF:

0.495

AC:

20473

AN:

41358

Ashkenazi Jewish (ASJ)

AF:

0.234

AC:

5262

AN:

22446

East Asian (EAS)

AF:

0.165

AC:

6483

AN:

39234

South Asian (SAS)

AF:

0.179

AC:

13839

AN:

77444

European-Finnish (FIN)

AF:

0.314

AC:

15414

AN:

49120

Middle Eastern (MID)

AF:

0.246

AC:

1354

AN:

5512

European-Non Finnish (NFE)

AF:

0.267

AC:

289259

AN:

1083136

Other (OTH)

AF:

0.277

AC:

16095

AN:

58140

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

16334

32668

49002

65336

81670

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9956

19912

29868

39824

49780

<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:

0.339

AC:

51594

AN:

152162

Hom.:

9477

Cov.:

AF XY:

0.342

AC XY:

25439

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.458

AC:

19008

AN:

41484

American (AMR)

AF:

0.435

AC:

6651

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.240

AC:

835

AN:

3472

East Asian (EAS)

AF:

0.219

AC:

1134

AN:

5178

South Asian (SAS)

AF:

0.164

AC:

791

AN:

4826

European-Finnish (FIN)

AF:

0.325

AC:

3440

AN:

10586

Middle Eastern (MID)

AF:

0.184

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.276

AC:

18793

AN:

68002

Other (OTH)

AF:

0.309

AC:

652

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1722

3445

5167

6890

8612

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

486

972

1458

1944

2430

<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:

0.205

Hom.:

746

Bravo

AF:

0.354

Asia WGS

AF:

0.191

AC:

662

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

7.5

(source)

DANN

Benign

0.83

PhyloP100

0.036

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over