11-118894558-G-C

Variant names:

• chr11-118894558-G-C
• rs598207
• NM_001716.5:c.1014G>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001716.5(CXCR5):​c.1014G>C​(p.Thr338Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 1,561,110 control chromosomes in the GnomAD database, including 64,566 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.34 (9477 hom., cov: 33)
  • Exomes 𝑓: 0.27 (55089 hom.)
• Consequence: CXCR5 NM_001716.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0360
• Publications: 21 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP7: Synonymous conserved (PhyloP=0.036 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCR5	NM_001716.5	c.1014G>C	p.Thr338Thr	synonymous_variant	Exon 2 of 2	ENST00000292174.5	NP_001707.1
CXCR5	NM_032966.2	c.879G>C	p.Thr293Thr	synonymous_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.1014G>C	p.Thr338Thr	synonymous_variant	Exon 2 of 2	1	NM_001716.5	ENSP00000292174.4
BCL9L	ENST00000334801.7	c.*3857C>G		3_prime_UTR_variant	Exon 8 of 8	1		ENSP00000335320.3

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51503 AN: 152044 Hom.: 9436 Cov.: 33

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.325

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.312

GnomAD2 exomes AF: 0.309 AC: 65482 AN: 211768 AF XY: 0.295

Gnomad AFR exome AF: 0.453

Gnomad AMR exome AF: 0.504

Gnomad ASJ exome AF: 0.240

Gnomad EAS exome AF: 0.229

Gnomad FIN exome AF: 0.320

Gnomad NFE exome AF: 0.271

Gnomad OTH exome AF: 0.278

GnomAD4 exome AF: 0.272 AC: 382938 AN: 1408948 Hom.: 55089 Cov.: 35 AF XY: 0.268 AC XY: 185882 AN XY: 693688

African (AFR) AF: 0.453 AC: 14759 AN: 32558

American (AMR) AF: 0.495 AC: 20473 AN: 41358

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 5262 AN: 22446

East Asian (EAS) AF: 0.165 AC: 6483 AN: 39234

South Asian (SAS) AF: 0.179 AC: 13839 AN: 77444

European-Finnish (FIN) AF: 0.314 AC: 15414 AN: 49120

Middle Eastern (MID) AF: 0.246 AC: 1354 AN: 5512

European-Non Finnish (NFE) AF: 0.267 AC: 289259 AN: 1083136

Other (OTH) AF: 0.277 AC: 16095 AN: 58140

GnomAD4 genome AF: 0.339 AC: 51594 AN: 152162 Hom.: 9477 Cov.: 33 AF XY: 0.342 AC XY: 25439 AN XY: 74376

African (AFR) AF: 0.458 AC: 19008 AN: 41484

American (AMR) AF: 0.435 AC: 6651 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 835 AN: 3472

East Asian (EAS) AF: 0.219 AC: 1134 AN: 5178

South Asian (SAS) AF: 0.164 AC: 791 AN: 4826

European-Finnish (FIN) AF: 0.325 AC: 3440 AN: 10586

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.276 AC: 18793 AN: 68002

Other (OTH) AF: 0.309 AC: 652 AN: 2110

Alfa AF: 0.205 Hom.: 746

Bravo AF: 0.354

Asia WGS AF: 0.191 AC: 662 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	7.5
DANN	Benign	0.83
PhyloP100		0.036
Mutation Taster		=100/0	polymorphism (auto)

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: rs598207; hg19: chr11-118765267; COSMIC: COSV52682665; COSMIC: COSV52682665;