rs1591967725

Variant names:

• chr11-118893806-A-C
• rs1591967725
• NM_001716.5:c.262A>C

Your query was ambiguous. Multiple possible variants found:

• chr11-118893806-A-C
• chr11-118893806-A-G
• chr11-118893806-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001716.5(CXCR5):​c.262A>C​(p.Thr88Pro) 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 pathogenic 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. T88N) 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: 2.94
• Publications: 0 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.85

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCR5	NM_001716.5	c.262A>C	p.Thr88Pro	missense_variant	Exon 2 of 2	ENST00000292174.5	NP_001707.1
CXCR5	NM_032966.2	c.127A>C	p.Thr43Pro	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.262A>C	p.Thr88Pro	missense_variant	Exon 2 of 2	1	NM_001716.5	ENSP00000292174.4
BCL9L	ENST00000334801.7	c.*4609T>G		downstream_gene_variant		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	Pathogenic	0.64
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.62	T
M_CAP	Uncertain	0.21	D
MetaRNN	Pathogenic	0.85	D
MetaSVM	Uncertain	0.088	D
MutationAssessor	Benign	1.9	L
PhyloP100		2.9
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.61
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.059	T
Polyphen		1.0	D
Vest4		0.48
MutPred		0.81		Loss of stability (P = 0.1017);
MVP		0.89
MPC		2.1
ClinPred		0.96	D
GERP RS		3.9
Varity_R		0.65
gMVP		0.72
Mutation Taster		=71/29	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: rs1591967725; hg19: chr11-118764515;