11-118893899-A-G

Position:

• chr11-118893899-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001716.5(CXCR5):​c.355A>G​(p.Thr119Ala) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CXCR5 NM_001716.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.93

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14719668).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CXCR5	NM_001716.5	c.355A>G	p.Thr119Ala	missense_variant	2/2	ENST00000292174.5	NP_001707.1
CXCR5	NM_032966.2	c.220A>G	p.Thr74Ala	missense_variant	1/1		NP_116743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CXCR5	ENST00000292174.5	c.355A>G	p.Thr119Ala	missense_variant	2/2	1	NM_001716.5	ENSP00000292174	P1
BCL9L	ENST00000334801.7	c.*4516T>C		3_prime_UTR_variant	8/8	1		ENSP00000335320	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 12, 2023

The c.355A>G (p.T119A) alteration is located in exon 2 (coding exon 2) of the CXCR5 gene. This alteration results from a A to G substitution at nucleotide position 355, causing the threonine (T) at amino acid position 119 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	11
DANN	Benign	0.95
DEOGEN2	Benign	0.35	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.3	L
MutationTaster	Benign	1.0	D;N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.13
Sift	Benign	0.085	T
Sift4G	Benign	0.23	T
Polyphen		0.0040	B
Vest4		0.029
MutPred		0.51		Loss of helix (P = 0.1706);
MVP		0.72
MPC		0.75
ClinPred		0.091	T
GERP RS		2.8
Varity_R		0.087
gMVP		0.055

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-118764608; COSMIC: COSV99418317; COSMIC: COSV99418317;