11-118894565-G-T

Variant names:

• chr11-118894565-G-T
• rs1038959105
• NM_001716.5:c.1021G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001716.5(CXCR5):​c.1021G>T​(p.Gly341Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000347 in 1,555,662 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000037 (0 hom.)
• Consequence: CXCR5 NM_001716.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.02

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 -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 52 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCR5	NM_001716.5	c.1021G>T	p.Gly341Cys	missense_variant	Exon 2 of 2	ENST00000292174.5	NP_001707.1
CXCR5	NM_032966.2	c.886G>T	p.Gly296Cys	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.1021G>T	p.Gly341Cys	missense_variant	Exon 2 of 2	1	NM_001716.5	ENSP00000292174.4
BCL9L	ENST00000334801	c.*3850C>A		3_prime_UTR_variant	Exon 8 of 8	1		ENSP00000335320.3

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152234 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000145 AC: 3 AN: 207532 AF XY: 0.0000274

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000316

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000371 AC: 52 AN: 1403428 Hom.: 0 Cov.: 32 AF XY: 0.0000391 AC XY: 27 AN XY: 690580

Gnomad4 AFR exome AF: 0.00 AC: 0 AN: 32286

Gnomad4 AMR exome AF: 0.00 AC: 0 AN: 40066

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 22082

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39190

Gnomad4 SAS exome AF: 0.00 AC: 0 AN: 76878

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 48842

Gnomad4 NFE exome AF: 0.0000481 AC: 52 AN: 1080716

Gnomad4 Remaining exome AF: 0.00 AC: 0 AN: 57900

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152234 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74366

Gnomad4 AFR AF: 0.0000241 AC: 0.0000241208 AN: 0.0000241208

Gnomad4 AMR AF: 0.00 AC: 0 AN: 0

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.0000147 AC: 0.0000146968 AN: 0.0000146968

Gnomad4 OTH AF: 0.00 AC: 0 AN: 0

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000227

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 30, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1021G>T (p.G341C) alteration is located in exon 2 (coding exon 2) of the CXCR5 gene. This alteration results from a G to T substitution at nucleotide position 1021, causing the glycine (G) at amino acid position 341 to be replaced by a cysteine (C). 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	Uncertain	0.36
BayesDel_addAF	Uncertain	0.045	T
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.42	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.77	T
M_CAP	Uncertain	0.089	D
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.6	L
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-5.9	D
REVEL	Uncertain	0.39
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.56
MutPred		0.40		Gain of helix (P = 0.132);
MVP		0.74
MPC		1.9
ClinPred		0.85	D
GERP RS		4.2
Varity_R		0.67
gMVP		0.83
Mutation Taster		=20/80	disease causing

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: rs1038959105; hg19: chr11-118765274;