rs373222312

Variant names:

• chr11-118894398-C-A
• rs373222312
• NM_001716.5:c.854C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-118894398-C-A
• chr11-118894398-C-G
• chr11-118894398-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001716.5(CXCR5):​c.854C>A​(p.Ala285Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A285G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CXCR5 NM_001716.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0890
• Publications: 7 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07785764).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCR5	NM_001716.5	c.854C>A	p.Ala285Glu	missense_variant	Exon 2 of 2	ENST00000292174.5	NP_001707.1
CXCR5	NM_032966.2	c.719C>A	p.Ala240Glu	missense_variant	Exon 1 of 1		NP_116743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCR5	ENST00000292174.5	c.854C>A	p.Ala285Glu	missense_variant	Exon 2 of 2	1	NM_001716.5	ENSP00000292174.4
BCL9L	ENST00000334801.7	c.*4017G>T		3_prime_UTR_variant	Exon 8 of 8	1		ENSP00000335320.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	3.2
DANN	Benign	0.81
DEOGEN2	Benign	0.080	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.078	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.29	N
PhyloP100		-0.089
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.22	N
REVEL	Benign	0.20
Sift	Benign	0.57	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.070
MutPred		0.71		Loss of ubiquitination at K288 (P = 0.1166);
MVP		0.47
MPC		0.89
ClinPred		0.034	T
GERP RS		-1.5
Varity_R		0.074
gMVP		0.45
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs373222312; hg19: chr11-118765107;