11-118893704-G-C

Variant names:

• chr11-118893704-G-C
• rs148564775
• NM_001716.5:c.160G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001716.5(CXCR5):​c.160G>C​(p.Val54Leu) 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. 16/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V54M) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CXCR5 NM_001716.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.040172607).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCR5	NM_001716.5	c.160G>C	p.Val54Leu	missense_variant	Exon 2 of 2	ENST00000292174.5	NP_001707.1
CXCR5	NM_032966.2	c.25G>C	p.Val9Leu	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.160G>C	p.Val54Leu	missense_variant	Exon 2 of 2	1	NM_001716.5	ENSP00000292174.4
BCL9L	ENST00000334801.7	c.*4711C>G		downstream_gene_variant		1		ENSP00000335320.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	12
DANN	Benign	0.70
DEOGEN2	Benign	0.075	T
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.34	N
PhyloP100		1.1
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.060	N
REVEL	Benign	0.033
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.063
MutPred		0.37		Loss of catalytic residue at V54 (P = 0.0883);
MVP		0.25
MPC		0.75
ClinPred		0.026	T
GERP RS		0.040
Varity_R		0.040
gMVP		0.31
Mutation Taster		=97/3	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: rs148564775; hg19: chr11-118764413;