rs3922

Positions:

• chr11-118894891-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
CXCR5	NM_001716.5	c.*228A>G		3_prime_UTR_variant	2/2	ENST00000292174.5	NP_001707.1
CXCR5	NM_032966.2	c.*228A>G		3_prime_UTR_variant	1/1		NP_116743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CXCR5	ENST00000292174.5	c.*228A>G		3_prime_UTR_variant	2/2	1	NM_001716.5	ENSP00000292174	P1
BCL9L	ENST00000334801.7	c.*3524T>C		3_prime_UTR_variant	8/8	1		ENSP00000335320	P4

Frequencies

GnomAD3 genomes AF: 0.483 AC: 73290 AN: 151886 Hom.: 18632 Cov.: 32

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.: 4 AF XY: 0.404 AC XY: 61932 AN XY: 153134

Gnomad4 AFR exome AF: 0.624

Gnomad4 AMR exome AF: 0.560

Gnomad4 ASJ exome AF: 0.439

Gnomad4 EAS exome AF: 0.225

Gnomad4 SAS exome AF: 0.251

Gnomad4 FIN exome AF: 0.424

Gnomad4 NFE exome AF: 0.408

Gnomad4 OTH exome AF: 0.442

GnomAD4 genome AF: 0.483 AC: 73386 AN: 152004 Hom.: 18682 Cov.: 32 AF XY: 0.482 AC XY: 35771 AN XY: 74282

Gnomad4 AFR AF: 0.636

Gnomad4 AMR AF: 0.547

Gnomad4 ASJ AF: 0.442

Gnomad4 EAS AF: 0.303

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.436

Gnomad4 NFE AF: 0.416

Gnomad4 OTH AF: 0.468

Alfa AF: 0.429 Hom.: 31336

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
DANN	Benign	0.24

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

Other links and lift over

dbSNP: rs3922; hg19: chr11-118765600; COSMIC: COSV52685125; COSMIC: COSV52685125;